greenmedinfo--2020-12-18--Synergistic interaction of eugenol and antimicrobial drugs in eradication of single and mixed biofil

Synergistic interaction of eugenol and antimicrobial drugs in eradication of single and mixed biofilms of Candida albicans and Streptococcus mutans.

In vitro eradication of the C. albicans and S. mutans mixed biofilms by eugenol alone and in combination with the @ @ @ @ @ strains of C. albicans ( CAJ-01 and CAJ-12 ) and S. mutans MTCC497 were used @ @ @ @ @ biofilms using XTT reduction assay , viability assay , time dependent killing assay and scanning @ @ @ @ @ .
Synergistic interaction was assessed by checkerboard method .
Sessile MIC ( SMIC ) of @ @ @ @ @ planktonic MIC ( PMIC ) against C. albicans and S. mutans mixed biofilms .
SMIC @ @ @ @ @ increased upto 1000-folds over PMIC .
Eradication of single or mixed biofilms was evident from @ @ @ @ @ .
At 1 × MIC of eugenol , logCFU count of C. albicans cells were @ @ @ @ @ and 3.8 ( p

In vitro eradication of the C. albicans and S. mutans mixed biofilms by eugenol alone and in combination with the antimicrobial drugs. Previously characterized strains of C. albicans (CAJ-01 and CAJ-12) and S. mutans MTCC497 were used to evaluate the eradication of biofilms using XTT reduction assay, viability assay, time dependent killing assay and scanning electron microscopy (SEM). Synergistic interaction was assessed by checkerboard method. Sessile MIC (SMIC) of eugenol was equivalent to the planktonic MIC (PMIC) against C. albicans and S. mutans mixed biofilms. SMIC of fluconazole and azithromycin was increased upto 1000-folds over PMIC. Eradication of single or mixed biofilms was evident from the viability assay and SEM. At 1 × MIC of eugenol, logCFU count of C. albicans cells were decreased from 6.3 to 4.2 and 3.8 (p < 0.05) in single and mixed biofilms, respectively. SEM studies revealed the eradication of C. albicans and S. mutans cells from glass surface at 800 µg/mL concentration of eugenol. Time dependent killing assay showed dose dependent effect of eugenol on pre-formed CAJ-01, CAJ-12 and S. mutans biofilm cells. Eugenol was highly synergistic with fluconazole (FICI = 0.156) against CAJ-12 single biofilms. However, the combination of eugenol and azithromycin showed maximum synergy (FICI = 0.140) against pre-formed C. albicans and S. mutans mixed biofilms. These findings highlighted the promising efficacy of eugenol in the eradication of biofilms of two oral pathogens (C. albicans and S. mutans) in vitro and could also be exploited in synergy with fluconazole and azithromycin in controlling oral infections.


greenmedinfo--2020-12-18--Eugenol disrupts Plasmodium falciparum intracellular development during the erythrocytic cycle and p

Eugenol disrupts Plasmodium falciparum intracellular development during the erythrocytic cycle and protects against cerebral malaria.

BACKGROUND : Malaria is a parasitic disease that compromises the human host .
Currently , control of the Plasmodium falciparum burden is centered on artemisinin-based combination therapies .
However , decreased sensitivity to artemisinin and derivatives has been reported , therefore it is important to identify new therapeutic strategies .
METHOD : We used human erythrocytes infected with P. falciparum and experimental cerebral malaria ( ECM ) animal model to assess the potential antimalarial effect of eugenol , a component of clove bud essential oil .
RESULTS : Plasmodium falciparum cultures treated with increasing concentrations of eugenol reduced parasitemia in @ @ @ @ @ @ @ ± 29.55 μM .
This effect seems to be irreversible and maintained even in the presence of high parasitemia .
The prominent effect of eugenol was detected in the evolution from schizont to ring forms , inducing important morphological changes , indicating a disruption in the development of the erythrocytic cycle .
Aberrant structural modification was observed by electron microscopy , showing the separation of the two nuclear membrane leaflets as well as other subcellular membranes , such as from the digestive vacuole .
Importantly , in vivo studies using ECM revealed a @ @ @ @ @ @ @ when mice were treated for 6 consecutive days upon infection .
CONCLUSIONS : These data suggest a potential effect of eugenol against Plasmodium sp .
with an impact on cerebral malaria .
GENERAL SIGNIFICANCE : Our results provide a rational basis for the use of eugenol in therapeutic strategies to the treatment of malaria .

BACKGROUND: Malaria is a parasitic disease that compromises the human host. Currently, control of the Plasmodium falciparum burden is centered on artemisinin-based combination therapies. However, decreased sensitivity to artemisinin and derivatives has been reported, therefore it is important to identify new therapeutic strategies.
METHOD: We used human erythrocytes infected with P. falciparum and experimental cerebral malaria (ECM) animal model to assess the potential antimalarial effect of eugenol, a component of clove bud essential oil.
RESULTS: Plasmodium falciparum cultures treated with increasing concentrations of eugenol reduced parasitemia in a dose-dependent manner, with ICof 532.42 ± 29.55 μM. This effect seems to be irreversible and maintained even in the presence of high parasitemia. The prominent effect of eugenol was detected in the evolution from schizont to ring forms, inducing important morphological changes, indicating a disruption in the development of the erythrocytic cycle. Aberrant structural modification was observed by electron microscopy, showing the separation of the two nuclear membrane leaflets as well as other subcellular membranes, such as from the digestive vacuole. Importantly, in vivo studies using ECM revealed a reduction in blood parasitemia and cerebral edema when mice were treated for 6 consecutive days upon infection.
CONCLUSIONS: These data suggest a potential effect of eugenol against Plasmodium sp. with an impact on cerebral malaria.
GENERAL SIGNIFICANCE: Our results provide a rational basis for the use of eugenol in therapeutic strategies to the treatment of malaria.


greenmedinfo--2020-12-18--A low dose of eugenol has antiulcer potential.

This study evaluated the gastric healing activity of eugenol , the main bioactive compound from clove ( Syzygium aromaticun ) essential oil .
Five groups of female Wistar rats were submitted to acetic acid-induced ulcer model and treated with Vehicle ( 1 mL/kg , p.o . )
, eugenol ( 1 , 10 or 100 mg/kg , p.o ) or omeprazole ( 20 mg/kg , p.o ) , twice a day , by seven or fourteen days .
Macroscopic , microscopic and biochemical analyses were performed in the ulcerated site .
Eugenol ( 1 mg/kg , p.o ) administered by @ @ @ @ @ @ @ healing process by 33 % and 52 % , respectively .
The healing actions of eugenol were accompanied by the rescue on the histological architecture and the normalization of the superoxide dismutase and catalase activity .
Moreover , eugenol ( 1 mg/kg , p.o ) reduced the gastric mucosal myeloperoxidase activity and increased the mucin secretion .
In contrast , eugenol at a dose of 100 mg/kg administered by 7 days enhanced 49 % the ulcerated area , but at 10 mg/kg did not change the ulcer area after 7 or 14 days @ @ @ @ @ @ @ undesirable results due to the worsening of the gastric lesion with the use of eugenol in high doses , the antiulcer potential of this compound is evident and manageable in an adequate dose .

This study evaluated the gastric healing activity of eugenol, the main bioactive compound from clove (Syzygium aromaticun) essential oil. Five groups of female Wistar rats were submitted to acetic acid-induced ulcer model and treated with Vehicle (1 mL/kg, p.o.), eugenol (1, 10 or 100 mg/kg, p.o) or omeprazole (20 mg/kg, p.o), twice a day, by seven or fourteen days. Macroscopic, microscopic and biochemical analyses were performed in the ulcerated site. Eugenol (1 mg/kg, p.o) administered by 7 or 14 days accelerated the gastric healing process by 33% and 52%, respectively. The healing actions of eugenol were accompanied by the rescue on the histological architecture and the normalization of the superoxide dismutase and catalase activity. Moreover, eugenol (1 mg/kg, p.o) reduced the gastric mucosal myeloperoxidase activity and increased the mucin secretion. In contrast, eugenol at a dose of 100 mg/kg administered by 7 days enhanced 49% the ulcerated area, but at 10 mg/kg did not change the ulcer area after 7 or 14 days of treatment. Thus, despite the undesirable results due to the worsening of the gastric lesion with the use of eugenol in high doses, the antiulcer potential of this compound is evident and manageable in an adequate dose.


greenmedinfo--2020-12-18--Red-jambo peel extract shows antiproliferative activity against HepG2 human hepatoma cells.

The peel of the red-jambo concentrates the majority of the bioactive compounds and antioxidant capacity of the fruit .
Minor phenolic compounds in this part of the fruit are still unknown , as well as the effect of its extracts in in vitro and in vivo studies .
In an ethanolic extract of red-jambo , a wider range of phenolic compounds was investigated and the antioxidant cellular antioxidant activity and inhibition of HepG2 cell proliferation were evaluated for the first time .
Using HPLC-FLD/DAD for phenolic compounds determination , gallic acid , chlorogenic acid and ( - ) -epigallocatechin gallate @ @ @ @ @ @ @ the peel of the red-jambo fruit .
The anthocyanins found ( cyanidin 3,5-diglucoside , cyanidin 3-glucoside and peonidin 3-glucoside ) were the flavonoid class strongly correlated with the antioxidant capacity methods used in this study ( cellular antioxidant activity and oxygen radical absorbance capacity ) .
The ethanolic extract of the peel showed significant effect on reducing the tumoral cell growth and proliferation .
Antiproliferative activity of phytochemicals showed no significant correlative relations with total phenolic compounds , flavonoids and anthocyanins , demonstrating which the antiproliferative effect of the extract could be due @ @ @ @ @ @ @ in red-jambo peel .

The peel of the red-jambo concentrates the majority of the bioactive compounds and antioxidant capacity of the fruit. Minor phenolic compounds in this part of the fruit are still unknown, as well as the effect of its extracts in in vitro and in vivo studies. In an ethanolic extract of red-jambo, a wider range of phenolic compounds was investigated and the antioxidant cellular antioxidant activity and inhibition of HepG2 cell proliferation were evaluated for the first time. Using HPLC-FLD/DAD for phenolic compounds determination, gallic acid, chlorogenic acid and (-)-epigallocatechin gallate were found for the first time in the peel of the red-jambo fruit. The anthocyanins found (cyanidin 3,5-diglucoside, cyanidin 3-glucoside and peonidin 3-glucoside) were the flavonoid class strongly correlated with the antioxidant capacity methods used in this study (cellular antioxidant activity and oxygen radical absorbance capacity). The ethanolic extract of the peel showed significant effect on reducing the tumoral cell growth and proliferation. Antiproliferative activity of phytochemicals showed no significant correlative relations with total phenolic compounds, flavonoids and anthocyanins, demonstrating which the antiproliferative effect of the extract could be due to the synergic action among the compounds in red-jambo peel.


greenmedinfo--2020-12-18--Protective effects of hydroalcoholic extracts from an ancient apple variety 'Mela Rosa dei Monti Sib

Protective effects of hydroalcoholic extracts from an ancient apple variety 'Mela Rosa dei Monti Sibillini' against renal ischemia/reperfusion injury.

The purpose of this work was to investigate the effect of hydroalcoholic extracts from the peel ( APE ) and @ @ @ @ @ a traditional apple variety of central Italy , the 'Mela Rosa dei Monti Sibillini ' @ @ @ @ @ by renal ischemia/reperfusion injury ( IRI ) in rats .
Thirty mg per kg b.w @ @ @ @ @ administered intraperitoneally to male adult Wistar rats 3 days before the induction of IRI by @ @ @ @ @ decrease in the levels of malondialdehyde ( MDA ) , tumor necrosis factor-α ( TNFα @ @ @ @ @ ( IL-1β ) and nuclear factor-κB ( NF-κB ) was observed in the groups pre-treated @ @ @ @ @ IRI rats .
The chemical composition of APE was determined by HPLC-DAD-MShighlighting a significant amount @ @ @ @ @ g ) , flavonols ( 42.27 mg g ) and dihydrochalcones ( 11.75 mg g @ @ @ @ @ that this ancient apple variety is a promising source of nutraceuticals and functional foods helpful @ @ @ @ @ disorders .

The purpose of this work was to investigate the effect of hydroalcoholic extracts from the peel (APE) and pulp (APP) of a traditional apple variety of central Italy, the 'Mela Rosa dei Monti Sibillini', on the damage caused by renal ischemia/reperfusion injury (IRI) in rats. Thirty mg per kg b.w. of the extracts were administered intraperitoneally to male adult Wistar rats 3 days before the induction of IRI by pedicle clamping. A significant decrease in the levels of malondialdehyde (MDA), tumor necrosis factor-α (TNFα), interleukin 1 beta (IL-1β) and nuclear factor-κB (NF-κB) was observed in the groups pre-treated with APE when compared with IRI rats. The chemical composition of APE was determined by HPLC-DAD-MShighlighting a significant amount of proanthocyanidins (52.9 mg g), flavonols (42.27 mg g) and dihydrochalcones (11.75 mg g). These findings indicated that this ancient apple variety is a promising source of nutraceuticals and functional foods helpful to manage complications of renal disorders.


greenmedinfo--2020-12-18--This study suggests that T. mongolicum protects against S. aureus-infected mastitis.

ETHNOPHARMACOLOGICAL RELEVANCE : As a traditional Chinese medicine , Taraxacum mongolicum has been widely used for the prevention and treatment of a variety of inflammatory and infectious diseases , and also clinically used as a remedy for mastitis .
However , the scientific rationale and mechanism behind its use on mastitis in vivo are still unclear .
AIM OF THE STUDY : This study aimed to investigate the protective effect and potential mechanism of Taraxacum mongolicum Hand.-Mazz .
( T. mongolicum ) on mastitis infected by Staphylococcus aureus ( S. aureus ) .
MATERIALS AND METHODS : Female ICR mice @ @ @ @ @ @ @ 10 g/kg of T. mongolicum extract twice per day for 6 consecutive days , and infected with S. aureus via teat canal to induce mastitis .
Pro-inflammatory cytokine tumor necrosis factor-α ( TNF-α ) , interleukin-6 ( IL-6 ) and interleukin-1β ( IL-1β ) levels were determined by ELISA .
Myeloperoxidase ( MPO ) activity and distribution were measured by reagent kit and immunohistochemistry .
Histopathological changes of mammary gland tissues were observed by H & E staining .
Toll-like receptor 2 ( TLR2 ) expression , phosphorylations of related proteins in nuclear @ @ @ @ @ @ @ protein kinases ( MAPKs ) signaling pathways were detected by western blot .
RESULTS : T. mongolicum decreased TNF-α , IL-6 and IL-1β levels , and reduced MPO activity and distribution in sera and mammary glands with S. aureus-infected mastitis .
In addition , T. mongolicum effectively attenuated histopathological damages and cell necrosis of mammary gland tissues infected by S. aureus .
Moreover , T. mongolicum inhibited the expression of TLR2 , and the phosphorylations of inhibitor κBα ( IκBα ) , p65 , p38 , extracellular signal-regulated kinase 1/2 ( ERK1/2 ) @ @ @ @ @ @ @ proteins in mammary glands with S. aureus-infected mastitis .
CONCLUSIONS : This study suggests that T. mongolicum protects against S. aureus-infected mastitis by exerting anti-inflammatory role , which is attributed to the inhibition of TLR2-NF-κB/MAPKs pathways .

ETHNOPHARMACOLOGICAL RELEVANCE: As a traditional Chinese medicine, Taraxacum mongolicum has been widely used for the prevention and treatment of a variety of inflammatory and infectious diseases, and also clinically used as a remedy for mastitis. However, the scientific rationale and mechanism behind its use on mastitis in vivo are still unclear.
AIM OF THE STUDY: This study aimed to investigate the protective effect and potential mechanism of Taraxacum mongolicum Hand.-Mazz. (T. mongolicum) on mastitis infected by Staphylococcus aureus (S. aureus).
MATERIALS AND METHODS: Female ICR mice were given intragastrically 2.5, 5 and 10 g/kg of T. mongolicum extract twice per day for 6 consecutive days, and infected with S. aureus via teat canal to induce mastitis. Pro-inflammatory cytokine tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) levels were determined by ELISA. Myeloperoxidase (MPO) activity and distribution were measured by reagent kit and immunohistochemistry. Histopathological changes of mammary gland tissues were observed by H&E staining. Toll-like receptor 2 (TLR2) expression, phosphorylations of related proteins in nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) signaling pathways were detected by western blot.
RESULTS: T. mongolicum decreased TNF-α, IL-6 and IL-1β levels, and reduced MPO activity and distribution in sera and mammary glands with S. aureus-infected mastitis. In addition, T. mongolicum effectively attenuated histopathological damages and cell necrosis of mammary gland tissues infected by S. aureus. Moreover, T. mongolicum inhibited the expression of TLR2, and the phosphorylations of inhibitor κBα (IκBα), p65, p38, extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK) proteins in mammary glands with S. aureus-infected mastitis.
CONCLUSIONS: This study suggests that T. mongolicum protects against S. aureus-infected mastitis by exerting anti-inflammatory role, which is attributed to the inhibition of TLR2-NF-κB/MAPKs pathways.


greenmedinfo--2020-12-18--Mechanistic study on inhibition of porcine pancreatic α-amylase using the flavonoids from dandelion.

This study was designed to investigate quantitatively the inhibition and molecular mechanism of pancreaticα-amylase exhibited by flavonoids from dandelion to @ @ @ @ @ relieving postprandial hyperglycemia .
The results show that the flavonoids reversibly inhibited the α-amylase in @ @ @ @ @ constant ( K ) and half-inhibitory concentration ( IC ) value of 10.51 and 0.0067 @ @ @ @ @ flavonoids present a strong ability to quench the intrinsic fluorescence of α-amylase through static quenching @ @ @ @ @ The values of the binding site ( n ) at different temperatures were found to @ @ @ @ @ indicating the presence of a singleclass of molecular binding of the dandelion flavonoids on α-amylase @ @ @ @ @ enthalpy and entropy change reveal that the binding was predominately driven by hydrophobic interactions .
@ @ @ @ @ of incorporating the dandelion flavonoids in making functional foods inmanaging the diet of the diabetes @

This study was designed to investigate quantitatively the inhibition and molecular mechanism of pancreaticα-amylase exhibited by flavonoids from dandelion to reveal its potential use in relieving postprandial hyperglycemia. The results show that the flavonoids reversibly inhibited the α-amylase in a non-competitive manner with Michaelis-Menten constant (K) and half-inhibitory concentration (IC) value of 10.51 and 0.0067 mg/mL, respectively. The flavonoids present a strong ability to quench the intrinsic fluorescence of α-amylase through static quenching by forming a complex. The values of the binding site (n) at different temperatures were found to be approximately the unity, indicating the presence of a singleclass of molecular binding of the dandelion flavonoids on α-amylase. The positive values of enthalpy and entropy change reveal that the binding was predominately driven by hydrophobic interactions. This study suggests a benefit of incorporating the dandelion flavonoids in making functional foods inmanaging the diet of the diabetes.


greenmedinfo--2020-12-18--Dandelion extract relaxes mouse airway smooth muscle by blocking VDLCC and NSCC channels.

BACKGROUND : Asthma is one of the main intractable diseases recognized by the international medical community .
The current widely used bronchodilators for asthma-β2-adrenal receptor agonists-have limited therapeutic effects , necessitating the development of novel antiasthma drugs with increased efficacy and fewer adverse effects .
In this study , we investigated the relaxant effects and underlying mechanism of an ethyl acetate extract from dandelion ( EAED ) onmouse airway smooth muscle .
METHODS : The effects of EAED on agonist-induced precontraction in mouse airway smooth muscle were evaluated with force measurement .
Mouse lung slices were used to study the @ @ @ @ @ @ @ .
The intracellular Caconcentration was measured using a calcium imaging system .
L-type voltage-dependent calcium channel ( VDLCC ) and non-selective cationic channel ( NSCC ) currents were measured by patch-clamp .
The lung functions of healthy and asthmatic mouse groups were assessed via the forced oscillation technique .
RESULTS : EAED inhibits acetylcholine-induced sustained contractions of whole airway smooth muscle by inhibiting VDLCCs , NSCCs , and some unknown channels , reduces the agonist-induced increase in the cytosolic free Caconcentration in airway smooth muscle cells , blocks VDLCC and NSCC currents , @ @ @ @ @ @ @ and asthmatic mice .
CONCLUSIONS : EAED may have potential beneficial effects on mitigating asthma attacks .

BACKGROUND: Asthma is one of the main intractable diseases recognized by the international medical community. The current widely used bronchodilators for asthma-β2-adrenal receptor agonists-have limited therapeutic effects, necessitating the development of novel antiasthma drugs with increased efficacy and fewer adverse effects. In this study, we investigated the relaxant effects and underlying mechanism of an ethyl acetate extract from dandelion (EAED) onmouse airway smooth muscle.
METHODS: The effects of EAED on agonist-induced precontraction in mouse airway smooth muscle were evaluated with force measurement. Mouse lung slices were used to study the effects of EAED on bronchial smooth muscle. The intracellular Caconcentration was measured using a calcium imaging system. L-type voltage-dependent calcium channel (VDLCC) and non-selective cationic channel (NSCC) currents were measured by patch-clamp. The lung functions of healthy and asthmatic mouse groups were assessed via the forced oscillation technique.
RESULTS: EAED inhibits acetylcholine-induced sustained contractions of whole airway smooth muscle by inhibiting VDLCCs, NSCCs, and some unknown channels, reduces the agonist-induced increase in the cytosolic free Caconcentration in airway smooth muscle cells, blocks VDLCC and NSCC currents, and relieves the respiratory resistance of healthy and asthmatic mice.
CONCLUSIONS: EAED may have potential beneficial effects on mitigating asthma attacks.


greenmedinfo--2020-12-18--Assessment synergistic effects of integrated therapy with epigallocatechin-3-gallate & arsenic triox

Assessment synergistic effects of integrated therapy with epigallocatechin-3-gallate & arsenic trioxide and irradiation on breast cancer cell line.

Background : Breast cancer is the most common invasive malignancy among women in the world .
The current breast cancer therapies pose significant clinical challenges .
Low-dose chemotherapy represents a new strategy to treat solid tumors in combination with natural products such as green tea catechins .
Epigallocatechin-3-gallate ( EGCG ) is the major polyphenolic extract from green tea with potent anticancer and antioxidant effects .
The purpose of this study was to investigate the effects of EGCG , Arsenic trioxide ( ATO ) and gamma radiation on MCF-7 cell line .
Methods : The anti-proliferative effects of EGCG and @ @ @ @ @ @ @ radiation on MCF-7 cells were evaluated with MTT assay .
The expression of apoptotic gens ( Bax , Bcl-2 , Caspase-3 and Fas ) was assessed by real-time PCR .
Results : Based on the results of MTT assay , EGCG and ATO exhibited dose and time-dependent anti-proliferative effects on MCF-7 cells .
The combined therapy of EGCG and ATO in presence and absence radiation could rise cell death up to 80 % .
Moreover , integrated therapy made Bax up-regulated and Bcl-2 down- regulated .
Conclusion : In assessment synergistic effects of @ @ @ @ @ @ @ irradiation had been significant impact on low dose chemotherapy for breast cancer treatment .

Background: Breast cancer is the most common invasive malignancy among women in the world. The current breast cancer therapies pose significant clinical challenges. Low-dose chemotherapy represents a new strategy to treat solid tumors in combination with natural products such as green tea catechins. Epigallocatechin-3-gallate (EGCG) is the major polyphenolic extract from green tea with potent anticancer and antioxidant effects. The purpose of this study was to investigate the effects of EGCG, Arsenic trioxide (ATO) and gamma radiation on MCF-7 cell line.
Methods: The anti-proliferative effects of EGCG and ATO individually, moreover in combination with radiation on MCF-7 cells were evaluated with MTT assay. The expression of apoptotic gens (Bax, Bcl-2, Caspase-3 and Fas) was assessed by real-time PCR.
Results: Based on the results of MTT assay, EGCG and ATO exhibited dose and time-dependent anti-proliferative effects on MCF-7 cells. The combined therapy of EGCG and ATO in presence and absence radiation could rise cell death up to 80%. Moreover, integrated therapy made Bax up-regulated and Bcl-2 down- regulated.
Conclusion: In assessment synergistic effects of integrated therapy with EGCG and ATO and irradiation had been significant impact on low dose chemotherapy for breast cancer treatment.


greenmedinfo--2020-12-18--Continuous intake of Matcha green tea effects exercise-induced metabolic responses by enhancing fat

Continuous intake of Matcha green tea effects exercise-induced metabolic responses by enhancing fat oxidation during moderate-intensity exercise.

Artificial green tea extracts may enhance exercise-induced fat oxidation .
Natural Matcha green tea consumption involves the ingestion of the powdered green tea leaves .
We examined the effects of three weeks daily intake of Matcha green tea powder on substrate oxidation during moderate-intensity exercise in females .
Females with a regular menstrual cycle ( =12 , age : 28±10yr , body mass : 69±17kg , height : 163±6cm ) volunteered to complete an incremental walking test to determine the individual moderate exercise intensity ( four metabolic equivalent ) for the subsequent 30-min treadmill walk .
The study had a @ @ @ @ @ @ @ between day 9 and 11 of the menstrual cycle ( follicular phase ) .
Participants consumed 3x1 gram capsules of Matcha premium grade , ( OMGTea Ltd , UK ) per day for three weeks , with the final dose ( 1 gram ) two hours before the 30-min walk ( walking speed : 5.8±0.4km·h ) .
Matcha had no effect on physiological responses ( e.g .
heart rate , placebo : 127±14 ; Matcha : 124±14 beats·min , =0.154 ) , but resulted in lower respiratory exchange ratio ( placebo : 0.872±0.040 @ @ @ @ @ @ @ ) , higher fat oxidation by 35±47 % ( placebo : 0.21±0.08 ; Matcha : 0.26±0.06 g·min ) ( =0.034 ) , and lower carbohydrate oxidation ( placebo : 0.75±0.21 ; Matcha : 0.60 ± 0.18 g·min ) ( = 0.048 ) during the 30-min moderate-intensity walk .
Energy expenditure was similar for both conditions .
There was no significant correlation between body fat % and the absolute or relative change in Matcha-induced fat oxidation during exercise .
Continuous intake of Matcha green tea effects exercise-induced metabolic responses by enhancing fat oxidation during @ @ @ @ @ @ @ independent of body composition .

Artificial green tea extracts may enhance exercise-induced fat oxidation. Natural Matcha green tea consumption involves the ingestion of the powdered green tea leaves. We examined the effects of three weeks daily intake of Matcha green tea powder on substrate oxidation during moderate-intensity exercise in females. Females with a regular menstrual cycle (=12, age: 28±10yr, body mass: 69±17kg, height: 163±6cm) volunteered to complete an incremental walking test to determine the individual moderate exercise intensity (four metabolic equivalent) for the subsequent 30-min treadmill walk. The study had a randomized placebo-controlled cross-over design with participants tested between day 9 and 11 of the menstrual cycle (follicular phase). Participants consumed 3x1 gram capsules of Matcha premium grade, (OMGTea Ltd, UK) per day for three weeks, with the final dose (1 gram) two hours before the 30-min walk (walking speed: 5.8±0.4km·h). Matcha had no effect on physiological responses (e.g. heart rate, placebo: 127±14; Matcha: 124±14 beats·min,=0.154), but resulted in lower respiratory exchange ratio (placebo: 0.872±0.040; Matcha: 0.839±0.035) (=0.033), higher fat oxidation by 35±47% (placebo: 0.21±0.08; Matcha: 0.26±0.06 g·min) (=0.034), and lower carbohydrate oxidation (placebo: 0.75±0.21; Matcha: 0.60 ± 0.18 g·min) ( = 0.048) during the 30-min moderate-intensity walk. Energy expenditure was similar for both conditions. There was no significant correlation between body fat % and the absolute or relative change in Matcha-induced fat oxidation during exercise. Continuous intake of Matcha green tea effects exercise-induced metabolic responses by enhancing fat oxidation during moderate-intensity exercise in adult females, seemingly independent of body composition.


greenmedinfo--2020-12-18--Matcha improves metabolic imbalance-induced cognitive dysfunction.

This study was conducted to assess the protective effect of extract of match ( EM ) on high-fat diet- ( HFD- ) induced cognitive deficits in male C57BL/6 mice .
It was found that EM improved glucose tolerance status by measuring OGTT and IPGTT with HFD-induced mice .
EM protected behavioral and memory dysfunction in Y-maze , passive avoidance , and Morris water maze tests .
Consumption of EM reduced fat mass , dyslipidemia , and inflammation in adipose tissue .
Also , EM ameliorated hepatic and cerebral antioxidant systems .
EM improved the cerebral cholinergic system by regulating ACh @ @ @ @ @ @ @ .
Also , EM restored mitochondrial function in liver and brain tissue .
EM attenuated hepatic inflammatory effect , lipid synthesis , and cholesterol metabolism by regulating the protein expression of TNF- , TNFR1 , -IRS-1 , -JNK , IL-1 , iNOS , COX-2 , HMGCR , PPAR , and FAS .
Finally , EM regulated cognitive function and neuroinflammation in the whole brain , hippocampus , and cerebral cortex by regulating the protein expression of-JNK , -Akt , -tau , A , BDNF , IDE , COX-2 , and IL-1 .
These @ @ @ @ @ @ @ potential source of functional food to improve metabolic disorder-associated cognitive dysfunction .

This study was conducted to assess the protective effect of extract of match (EM) on high-fat diet- (HFD-) induced cognitive deficits in male C57BL/6 mice. It was found that EM improved glucose tolerance status by measuring OGTT and IPGTT with HFD-induced mice. EM protected behavioral and memory dysfunction in Y-maze, passive avoidance, and Morris water maze tests. Consumption of EM reduced fat mass, dyslipidemia, and inflammation in adipose tissue. Also, EM ameliorated hepatic and cerebral antioxidant systems. EM improved the cerebral cholinergic system by regulating ACh contents and expression of AChE and ChAT. Also, EM restored mitochondrial function in liver and brain tissue. EM attenuated hepatic inflammatory effect, lipid synthesis, and cholesterol metabolism by regulating the protein expression of TNF-, TNFR1,-IRS-1,-JNK, IL-1, iNOS, COX-2, HMGCR, PPAR, and FAS. Finally, EM regulated cognitive function and neuroinflammation in the whole brain, hippocampus, and cerebral cortex by regulating the protein expression of-JNK,-Akt,-tau, A, BDNF, IDE, COX-2, and IL-1. These findings suggest that EM might be a potential source of functional food to improve metabolic disorder-associated cognitive dysfunction.


greenmedinfo--2020-12-18--Tanshinone IIA attenuates neuroinflammation via inhibiting RAGE/NF-κB signaling pathway in vivo and

Tanshinone IIA attenuates neuroinflammation via inhibiting RAGE/NF-κB signaling pathway in vivo and in vitro.

BACKGROUND : Glial activation and neuroinflammation play a crucial role in the pathogenesis and development of Alzheimer 's disease ( AD ) .
The receptor for advanced glycation end products ( RAGE ) -mediated signaling pathway is related to amyloid beta ( Aβ ) -induced neuroinflammation .
This study aimed to investigate the neuroprotective effects of tanshinone IIA ( tan IIA ) , a natural product isolated from traditional Chinese herbal Salvia miltiorrhiza Bunge , against Aβ-induced neuroinflammation , cognitive impairment , and neurotoxicity as well as theunderlying mechanisms in vivo and in vitro .
METHODS : Open-field test , @ @ @ @ @ @ @ test were conducted to assess the cognitive function in APP/PS1 mice .
Immunohistochemistry , immunofluorescence , thioflavin S ( Th-S ) staining , enzyme-linked immunosorbent assay ( ELISA ) , real-time quantitative reverse-transcription polymerase chain reaction ( qRT-PCR ) , and western blotting were performed to explore Aβ deposition , synaptic and neuronal loss , microglial and astrocytic activation , RAGE-dependent signaling , and the production of pro-inflammatory cytokines in APP/PS1 mice and cultured BV2 and U87 cells .
RESULTS : Tan IIA treatment prevented spatial learning and memory deficits in APP/PS1 mice @ @ @ @ @ @ @ accumulation , synapse-associated proteins ( Syn and PSD-95 ) and neuronal loss , as well as peri-plaque microgliosis and astrocytosis in the cortex and hippocampus of APP/PS1 mice .
Furthermore , tan IIA significantly suppressed RAGE/nuclear factor-κB ( NF-κB ) signaling pathway and the production ofpro-inflammatory cytokines ( TNF-α , IL-6 , and IL-1β ) in APP/PS1 mice and cultured BV2 and U87 cells .
CONCLUSIONS : Taken together , the present results indicated that tan IIA improves cognitive decline and neuroinflammation partly via inhibiting RAGE/NF-κB signaling pathway in vivo and in vitro @ @ @ @ @ @ @ a promising therapeutic drug for halting and preventing AD progression .

BACKGROUND: Glial activation and neuroinflammation play a crucial role in the pathogenesis and development of Alzheimer's disease (AD). The receptor for advanced glycation end products (RAGE)-mediated signaling pathway is related to amyloid beta (Aβ)-induced neuroinflammation. This study aimed to investigate the neuroprotective effects of tanshinone IIA (tan IIA), a natural product isolated from traditional Chinese herbal Salvia miltiorrhiza Bunge, against Aβ-induced neuroinflammation, cognitive impairment, and neurotoxicity as well as theunderlying mechanisms in vivo and in vitro.
METHODS: Open-field test, Y-maze test, and Morris water maze test were conducted to assess the cognitive function in APP/PS1 mice. Immunohistochemistry, immunofluorescence, thioflavin S (Th-S) staining, enzyme-linked immunosorbent assay (ELISA), real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR), and western blotting were performed to explore Aβ deposition, synaptic and neuronal loss, microglial and astrocytic activation, RAGE-dependent signaling, and the production of pro-inflammatory cytokines in APP/PS1 mice and cultured BV2 and U87 cells.
RESULTS: Tan IIA treatment prevented spatial learning and memory deficits in APP/PS1 mice. Additionally, tan IIA attenuated Aβ accumulation, synapse-associated proteins (Syn and PSD-95) and neuronal loss, as well as peri-plaque microgliosis and astrocytosis in the cortex and hippocampus of APP/PS1 mice. Furthermore, tan IIA significantly suppressed RAGE/nuclear factor-κB (NF-κB) signaling pathway and the production ofpro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) in APP/PS1 mice and cultured BV2 and U87 cells.
CONCLUSIONS: Taken together, the present results indicated that tan IIA improves cognitive decline and neuroinflammation partly via inhibiting RAGE/NF-κB signaling pathway in vivo and in vitro. Thus, tan IIA might be a promising therapeutic drug for halting and preventing AD progression.


greenmedinfo--2020-12-18--Tanshinone IIA exerts therapeutic effects by acting on endogenous stem cells in rats with liver cirr

Tanshinone IIA exerts therapeutic effects by acting on endogenous stem cells in rats with liver cirrhosis.

BACKGROUND AND OBJECTIVE : Liver cirrhosis ( LC ) , the major pathway for the progression and development of chronic liver disease , is an advanced stage of liver disease .
It is the third most common chronic noncommunicable disease after cardiovascular diseases and malignant tumors .
Tanshinone IIA ( Tan ) , an extract of Salvia miltiorrhiza ( S. miltiorrhiza ) , has been proven to promote the proliferation and differentiation of stem cells .
Moreover , its protective effect in liver injury has received widespread attention .
The present study investigated whether Tan plays a therapeutic role in @ @ @ @ @ @ @ and differentiation .
MATERIALS AND METHODS : LC models were established by intraperitoneal injection of an olive oil solution containing 50 % carbon tetrachloride ( CCL ) combined with 10 % alcohol in the drinking water .
After successful model establishment , the animals were randomly divided into four groups and injected with physiological saline or low- , medium- , or high-dose ( 10 , 20 , or 40 mg/kg ) Tan for seven consecutive days .
The protective effect of Tan on LC was observed by western blotting , serological examination and @ @ @ @ @ @ @ of 5-bromo-2-deoxyuridine ( BrdU ) and the liver cell markers albumin and CK-18 or the liver stem cell markers EPCAM and OV-6 was used to evaluate the proliferation and differentiation of endogenous liver stem cells .
RESULTS : We confirmed successful establishment of the LC model by observing transaminase levels and hematoxylin-eosin ( HE ) and Masson staining of liver sections in CCL-treated and healthy rats .
After Tan treatment , HE and Masson staining of paraffin sections of liver tissue showed that Tan treatment significantly improved histological injury to the liver .
@ @ @ @ @ @ @ ) scores and models for end-stage liver disease ( MELD ) were lower .
Immunofluorescence and immunohistochemical staining showed that the newly proliferated cells were colocalized with ALB , OV-6 , EPCAM , and CK-18 , indicating that new expression of these markers occurred after Tan injection .
All results were most significant in the medium-dose treatment group .
CONCLUSION : Tan can alleviate liver injury induced by CCLcombined with alcohol in rats and plays a therapeutic role in LC by promoting the proliferation and differentiation of endogenous liver stem cells .

BACKGROUND AND OBJECTIVE: Liver cirrhosis (LC), the major pathway for the progression and development of chronic liver disease, is an advanced stage of liver disease. It is the third most common chronic noncommunicable disease after cardiovascular diseases and malignant tumors. Tanshinone IIA (Tan), an extract of Salvia miltiorrhiza (S. miltiorrhiza), has been proven to promote the proliferation and differentiation of stem cells. Moreover, its protective effect in liver injury has received widespread attention. The present study investigated whether Tan plays a therapeutic role in LC by promoting endogenous stem cell proliferation and differentiation.
MATERIALS AND METHODS: LC models were established by intraperitoneal injection of an olive oil solution containing 50 % carbon tetrachloride (CCL) combined with 10 % alcohol in the drinking water. After successful model establishment, the animals were randomly divided into four groups and injected with physiological saline or low-, medium-, or high-dose (10, 20, or 40 mg/kg) Tan for seven consecutive days. The protective effect of Tan on LC was observed by western blotting, serological examination and histopathological staining. Furthermore, immunofluorescence double-labeling of 5-bromo-2-deoxyuridine (BrdU) and the liver cell markers albumin and CK-18 or the liver stem cell markers EPCAM and OV-6 was used to evaluate the proliferation and differentiation of endogenous liver stem cells.
RESULTS: We confirmed successful establishment of the LC model by observing transaminase levels and hematoxylin-eosin (HE) and Masson staining of liver sections in CCL-treated and healthy rats. After Tan treatment, HE and Masson staining of paraffin sections of liver tissue showed that Tan treatment significantly improved histological injury to the liver. Serological tests showed that albumin-bilirubin (ALBI) scores and models for end-stage liver disease (MELD) were lower. Immunofluorescence and immunohistochemical staining showed that the newly proliferated cells were colocalized with ALB, OV-6, EPCAM, and CK-18, indicating that new expression of these markers occurred after Tan injection. All results were most significant in the medium-dose treatment group.
CONCLUSION: Tan can alleviate liver injury induced by CCLcombined with alcohol in rats and plays a therapeutic role in LC by promoting the proliferation and differentiation of endogenous liver stem cells.


greenmedinfo--2020-12-18--Tanshinone IIA suppresses glioma cell oroliferation, migration and invasion.

Background : Tanshinone IIA ( TIIA ) is one of the active constituents derived from the rhizome of Danshen , a traditional Chinese herbal .
Recently , microRNAs ( miRNAs ) have been suggested to be associated with the anticancer role of TIIA .
However , it remains vague of the interaction between miRNAs and TIIA in glioma , a common aggressive brain tumor in humans .
Methods : Expression of miRNA ( miR ) -16-5p and talin-1 ( TLN1 ) was detected using reverse transcription-quantitative polymerase chain reaction and Western blotting .
Cell proliferation , migration and invasion were @ @ @ @ @ @ @ assay , Western blotting , and xenograft tumor experiment .
The target binding between miR-16-5p and TLN1 was confirmed by dual-luciferase reporter assay and RNA pull-down assay .
Results : TIIA treatment inhibited cell viability , migration and invasion , and decreased Cyclin D1 , matrix metalloproteinase ( MMP ) -9 and Vimentin expression in glioma T98G and A172 cells both in vitro and in vivo .
Thus , TIIA induced anti-glioma role , wherein miR-16-5p was upregulated and TLN1 was downregulated .
Moreover , silencing miR-16-5p could abate TIIA-mediated suppression on glioma @ @ @ @ @ @ @ vitro and in vivo .
TLN1 overexpression also exerted tumor-promoting effect in TIIA-treated T98G and A172 cells .
Mechanically , miR-16-5p could regulate TLN1 expression via target binding , and depleting TLN1 could counteract the inhibitory effect of miR-16-5p knockdown on the curative effect of TIIA in T98G and A172 cells .
Conclusion : TIIA exerted the anti-proliferation , anti-migration and anti-invasion role in glioma cells both in vitro and in vivo partially through regulating miR-16-5p/TLN1 axis .

Background: Tanshinone IIA (TIIA) is one of the active constituents derived from the rhizome of Danshen, a traditional Chinese herbal. Recently, microRNAs (miRNAs) have been suggested to be associated with the anticancer role of TIIA. However, it remains vague of the interaction between miRNAs and TIIA in glioma, a common aggressive brain tumor in humans.
Methods: Expression of miRNA (miR)-16-5p and talin-1 (TLN1) was detected using reverse transcription-quantitative polymerase chain reaction and Western blotting. Cell proliferation, migration and invasion were assessed with cell viability assay, transwell assay, Western blotting, and xenograft tumor experiment. The target binding between miR-16-5p and TLN1 was confirmed by dual-luciferase reporter assay and RNA pull-down assay.
Results: TIIA treatment inhibited cell viability, migration and invasion, and decreased Cyclin D1, matrix metalloproteinase (MMP)-9 and Vimentin expression in glioma T98G and A172 cells both in vitro and in vivo. Thus, TIIA induced anti-glioma role, wherein miR-16-5p was upregulated and TLN1 was downregulated. Moreover, silencing miR-16-5p could abate TIIA-mediated suppression on glioma cell proliferation, migration and invasion in vitro and in vivo. TLN1 overexpression also exerted tumor-promoting effect in TIIA-treated T98G and A172 cells. Mechanically, miR-16-5p could regulate TLN1 expression via target binding, and depleting TLN1 could counteract the inhibitory effect of miR-16-5p knockdown on the curative effect of TIIA in T98G and A172 cells.
Conclusion: TIIA exerted the anti-proliferation, anti-migration and anti-invasion role in glioma cells both in vitro and in vivo partially through regulating miR-16-5p/TLN1 axis.


greenmedinfo--2020-12-18--Tan IIA inhibits EMT and metastasis of colorectal cancer through repressing β-arrestin1-mediated β-c

Tan IIA inhibits EMT and metastasis of colorectal cancer through repressing β-arrestin1-mediated β-catenin signalling pathway.

Tanshinone IIA ( Tan IIA ) is a major active ingredient extracted from Salvia miltiorrhiza , which has been proved to be able to inhibit metastasis of various cancers including colorectal cancer ( CRC ) .
However , the mechanisms of anti-metastatic effect of Tan IIA on CRC are not well explored .
A number of studies indicate that epithelial-to-mesenchymal transition ( EMT ) plays an important role in CRC metastasis , and our previous studies demonstrate thatβ-arrestin1could regulate EMT in CRC partly through β-catenin signaling pathway .
In this work , we investigate whether Tan IIA could regulate EMT @ @ @ @ @ @ @ bothand .
Our results showed that Tan IIA inhibited lung metastases of CRC cellsand extended the survival time of mice with CRC.
, Tan IIA increased the expression of E-cadherin , decreased the expression of Snail , N-cadherin and Vimentin , thus suppressed EMT and the migratory ability of CRC cells .
Further study found that the mechanism of action of Tan IIA in regulating EMT and metastasis is associated with the suppression ofβ-arrestin1 expression , resulting in the increase of GSK-3β expression , reduction of β-catenin nuclear localization , thereby decreased the @ @ @ @ @ @ @ data revealed a new mechanism of Tan IIA on the suppression of EMT and metastasis in CRC via β-arrestin1-mediated β-catenin signaling pathway and provided support for using Tan IIA as anti-metastatic agents in CRC .

Tanshinone IIA (Tan IIA) is a major active ingredient extracted from Salvia miltiorrhiza, which has been proved to be able to inhibit metastasis of various cancers including colorectal cancer (CRC). However, the mechanisms of anti-metastatic effect of Tan IIA on CRC are not well explored. A number of studies indicate that epithelial-to-mesenchymal transition (EMT) plays an important role in CRC metastasis, and our previous studies demonstrate thatβ-arrestin1could regulate EMT in CRC partly through β-catenin signaling pathway. In this work, we investigate whether Tan IIA could regulate EMT in CRC through β-arrestin1-mediated β-catenin signaling pathway bothand. Our results showed that Tan IIA inhibited lung metastases of CRC cellsand extended the survival time of mice with CRC., Tan IIA increased the expression of E-cadherin, decreased the expression of Snail, N-cadherin and Vimentin, thus suppressed EMT and the migratory ability of CRC cells. Further study found that the mechanism of action of Tan IIA in regulating EMT and metastasis is associated with the suppression ofβ-arrestin1 expression, resulting in the increase of GSK-3β expression, reduction of β-catenin nuclear localization, thereby decreased the activity of β-catenin signaling pathway. Our data revealed a new mechanism of Tan IIA on the suppression of EMT and metastasis in CRC via β-arrestin1-mediated β-catenin signaling pathway and provided support for using Tan IIA as anti-metastatic agents in CRC.


greenmedinfo--2020-12-18--Prospective therapeutic potential of Tanshinone IIA: An updated overview.

In the past decades , the branch of complementary and alternative medicine based therapeutics has gained considerable attention worldwide .
@ @ @ @ @ medicinal plants , their products and/or product derivatives have been explored on an increasing scale @ @ @ @ @ IIA ) is a pharmacologically active lipophilic component of Salvia miltiorrhiza extract .
Tan IIA @ @ @ @ @ repute in Traditional Chinese Medicine .
Reckoning with these , the present review collates the @ @ @ @ @ with a special emphasis on its therapeutic potential against diverse diseases including cardiovascular diseases , @ @ @ @ @ diabetes , obesity and neurogenerative diseases .
Further , possible applications of various therapeutic preparations @ @ @ @ @ with special emphasis on nano-based drug delivery formulations .
Considering the tremendous advancement in the @ @ @ @ @ therapeutic potential of Tan IIA , the convergence of these two aspects can be foreseen @ @ @ @ @ application .

In the past decades, the branch of complementary and alternative medicine based therapeutics has gained considerable attention worldwide. Pharmacological efficacy of various traditional medicinal plants, their products and/or product derivatives have been explored on an increasing scale. Tanshinone IIA (Tan IIA) is a pharmacologically active lipophilic component of Salvia miltiorrhiza extract. Tan IIA shares a history of high repute in Traditional Chinese Medicine. Reckoning with these, the present review collates the pharmacological properties of Tan IIA with a special emphasis on its therapeutic potential against diverse diseases including cardiovascular diseases, cerebrovascular diseases, cancer, diabetes, obesity and neurogenerative diseases. Further, possible applications of various therapeutic preparations of Tan IIA were discussed with special emphasis on nano-based drug delivery formulations. Considering the tremendous advancement in the field of nanomedicine and the therapeutic potential of Tan IIA, the convergence of these two aspects can be foreseen with great promise in clinical application.


greenmedinfo--2020-12-18--Tanshinone IIA attenuates atherosclerosis via inhibiting NLRP3 inflammasome activation.

Tanshinone IIA ( Tan IIA ) possesses potent anti-atherogenic function , however , the underlying pharmacological mechanism remains incompletely understood .
Previous studies suggest that oxidized LDL ( oxLDL ) -induced NLRP3 ( NOD-like receptor ( NLR ) family , pyrin domain-containing protein 3 ) inflammasome activation in macrophages plays a vital role in atherogenesis .
Whether the anti-atherogenic effect of Tan IIA relies on the inhibition of the NLRP3 inflammasome has not been investigated before .
In this study , we found that Tan IIA treatment of high-fat diet fed ApoE-/- mice significantly attenuated NLRP3 inflammasome activation in vivo @ @ @ @ @ @ @ inhibited oxLDL-induced NLRP3 inflammasome activation in mouse macrophages .
Mechanically , Tan IIA inhibited NF-κB activation to downregulate pro-interleukin ( IL ) -1β and NLRP3 expression , and decreased oxLDL-induced expression of lectin-like oxidized LDL receptor-1 ( LOX-1 ) and cluster of differentiation 36 ( CD36 ) , thereby attenuating oxLDL cellular uptake and subsequent induction of mitochondrial and lysosomal damage - events that promote the NLRP3 inflammasome assembly .
Through regulating both the inflammasome 'priming ' and 'activation ' steps , Tan IIA potently inhibited oxLDL-induced NLRP3 inflammasome activation , thereby ameliorating @ @

Tanshinone IIA (Tan IIA) possesses potent anti-atherogenic function, however, the underlying pharmacological mechanism remains incompletely understood. Previous studies suggest that oxidized LDL (oxLDL)-induced NLRP3 (NOD-like receptor (NLR) family, pyrin domain-containing protein 3) inflammasome activation in macrophages plays a vital role in atherogenesis. Whether the anti-atherogenic effect of Tan IIA relies on the inhibition of the NLRP3 inflammasome has not been investigated before. In this study, we found that Tan IIA treatment of high-fat diet fed ApoE-/- mice significantly attenuated NLRP3 inflammasome activation in vivo. Consistently, Tan IIA also potently inhibited oxLDL-induced NLRP3 inflammasome activation in mouse macrophages. Mechanically, Tan IIA inhibited NF-κB activation to downregulate pro-interleukin (IL) -1β and NLRP3 expression, and decreased oxLDL-induced expression of lectin-like oxidized LDL receptor-1 (LOX-1) and cluster of differentiation 36 (CD36), thereby attenuating oxLDL cellular uptake and subsequent induction of mitochondrial and lysosomal damage - events that promote the NLRP3 inflammasome assembly. Through regulating both the inflammasome 'priming' and 'activation' steps, Tan IIA potently inhibited oxLDL-induced NLRP3 inflammasome activation, thereby ameliorating atherogenesis.


greenmedinfo--2020-12-19--Pancreatic cancer-targeting exosomes for enhancing immunotherapy and reprogramming tumor microenviro

Pancreatic cancer-targeting exosomes for enhancing immunotherapy and reprogramming tumor microenvironment.

Immunotherapy has gained increasing focus in treating pancreatic ductal adenocarcinoma ( PDAC ) , since conventional therapies like chemotherapy could not provide satisfactory improvement in overall survival outcome of PDAC patients .
However , it is still not the game changing solution due to the unique tumor microenvironment and low cancer immunogenicity of PDAC .
Thus , inducing more intratumoral effector immune cells as well as reversing immunosuppression is the core of PDAC treatment .
Herein , we demonstrate an exosome-based dual delivery biosystem for enhancing PDAC immunotherapy as well as reversing tumor immunosuppression of M2-like tumor associated macrophages ( @ @ @ @ @ @ @ axis .
The deliver system is constructed from bone marrow mesenchymal stem cell ( BM-MSC ) exosomes , electroporation-loaded galectin-9 siRNA , and surficially modified with oxaliplatin ( OXA ) prodrug as an immunogenic cell death ( ICD ) -trigger .
The use of biomaterials , BM-MSC exosomes , can significantly improve tumor targeting efficacy , thus increasing drug accumulation in the tumor site .
The combined therapy ( iEXO-OXA ) elicits anti-tumor immunity through tumor-suppressive macrophage polarization , cytotoxic T lymphocytes recruitment and Tregs downregulation , and achieves significant therapeutic efficacy in @ @ @

Immunotherapy has gained increasing focus in treating pancreatic ductal adenocarcinoma (PDAC), since conventional therapies like chemotherapy could not provide satisfactory improvement in overall survival outcome of PDAC patients. However, it is still not the game changing solution due to the unique tumor microenvironment and low cancer immunogenicity of PDAC. Thus, inducing more intratumoral effector immune cells as well as reversing immunosuppression is the core of PDAC treatment. Herein, we demonstrate an exosome-based dual delivery biosystem for enhancing PDAC immunotherapy as well as reversing tumor immunosuppression of M2-like tumor associated macrophages (M2-TAMs) upon disruption of galectin-9/dectin 1 axis. The deliver system is constructed from bone marrow mesenchymal stem cell (BM-MSC) exosomes, electroporation-loaded galectin-9 siRNA, and surficially modified with oxaliplatin (OXA) prodrug as an immunogenic cell death (ICD)-trigger. The use of biomaterials, BM-MSC exosomes, can significantly improve tumor targeting efficacy, thus increasing drug accumulation in the tumor site. The combined therapy (iEXO-OXA) elicits anti-tumor immunity through tumor-suppressive macrophage polarization, cytotoxic T lymphocytes recruitment and Tregs downregulation, and achieves significant therapeutic efficacy in cancer treatment.


greenmedinfo--2020-12-19--High-fat diet-mediated AMPKα1 inhibition promotes NAFLD by increasing numbers of AT CD36-containing

High-fat diet-mediated AMPKα1 inhibition promotes NAFLD by increasing numbers of AT CD36-containing exosomes.

Exosomes are important for intercellular communication , but the role of exosomes in the communication between adipose tissue ( AT ) and the liver remains unknown .
The aim of this study is to determine the contribution of AT-derived exosomes in nonalcoholic fatty liver disease ( NAFLD ) .
Exosome components , liver fat content , and liver function were monitored in AT in mice fed a high-fat diet ( HFD ) or treated with metformin- or GW4869 and with AMP-activated protein kinase ( AMPKα1 ) floxed/WT ) , , liver tissue-specific , or AT-specificmodification .
In cultured adipocytes and @ @ @ @ @ @ @ the absence ofincreased exosome release and exosomal proteins by elevating tumor susceptibility gene 101 ( ) -mediated exosome biogenesis .
In adipocytes treated with palmitic acid , TSG101 facilitated scavenger receptor class B ( CD36 ) sorting into exosomes .
CD36-containing exosomes were then endocytosed by hepatocytes to induce lipid accumulation and inflammation .
Consistently , an HFD induced more severe lipid accumulation and cell death inand adipose tissue-specificmice than in WT and liver-specificmice .
AMPK activation by metformin reduced adipocyte-mediated exosome release and mitigated fatty liver development in WT and liver specificmice @ @ @ @ @ @ @ inhibitor GW4869 blocked exosome secretion and alleviated HFD-induced fatty livers inand adipocyte-specificmice .
We conclude that HFD-mediated AMPKα1 inhibition promotes NAFLD by increasing numbers of AT CD36-containing exosomes .

Exosomes are important for intercellular communication, but the role of exosomes in the communication between adipose tissue (AT) and the liver remains unknown. The aim of this study is to determine the contribution of AT-derived exosomes in nonalcoholic fatty liver disease (NAFLD). Exosome components, liver fat content, and liver function were monitored in AT in mice fed a high-fat diet (HFD) or treated with metformin- or GW4869 and with AMP-activated protein kinase (AMPKα1) floxed/WT),, liver tissue-specific, or AT-specificmodification. In cultured adipocytes and white adipose tissue (WAT), the absence ofincreased exosome release and exosomal proteins by elevating tumor susceptibility gene 101 ()-mediated exosome biogenesis. In adipocytes treated with palmitic acid, TSG101 facilitated scavenger receptor class B (CD36) sorting into exosomes. CD36-containing exosomes were then endocytosed by hepatocytes to induce lipid accumulation and inflammation. Consistently, an HFD induced more severe lipid accumulation and cell death inand adipose tissue-specificmice than in WT and liver-specificmice. AMPK activation by metformin reduced adipocyte-mediated exosome release and mitigated fatty liver development in WT and liver specificmice. Moreover, administration of the exosome inhibitor GW4869 blocked exosome secretion and alleviated HFD-induced fatty livers inand adipocyte-specificmice. We conclude that HFD-mediated AMPKα1 inhibition promotes NAFLD by increasing numbers of AT CD36-containing exosomes.


greenmedinfo--2020-12-19--The exosomal transfer of macrophage-derived miR-223 conferred doxorubicin resistance in gastric canc

The exosomal transfer of macrophage-derived miR-223 conferred doxorubicin resistance in gastric cancer.

Purpose : Macrophages are a major component of the tumour microenvironment and play an important role in chemoresistance of cancer .
However , how exosomal microRNAs ( miRNAs ) derived from macrophages contribute to the development of doxorubicin resistance in gastric cancer ( GC ) are not clearly defined .
The aim of this study was to investigate whether macrophage-derived exosomes mediate doxorubicin resistance in GC .
Methods : Exosomes isolated from macrophage culture medium were characterized and co-cultured with GC cells and the miR-223 level was detected using real-time quantitative PCR ( RT-qPCR ) .
The internalization of exosomes @ @ @ @ @ @ @ immunofluorescence .
Macrophages were transfected with an miR-223 inhibitor or negative control .
Cell Counting Kit-8 and flow cytometry were employed to explore the effect of macrophage-derived exosomes on the doxorubicin resistance of GC cells .
Western blot and RT-qPCR assay were also performed to explore the regulation of GC chemotherapy resistance by exosomal miR-223 .
Results : Here , the macrophages and macrophage-derived exosomes promoted doxorubicin resistance in GC cells .
MiR-223 was enriched in macrophage-derived exosomes and they could be transferred to co-cultivated GC cells .
The miR-223 knockdown in macrophages @ @ @ @ @ @ @ GC cells .
Functional studies revealed that exosomal miR-223 derived from macrophages promoted doxorubicin resistance in GC cells by inhibiting F-box and WD repeat domain-containing 7 ( ) .
Clinically , the expression of miR-223 significantly increased in GC tissues and high expression of plasma exosomal miR-223 was highly linked with doxorubicin resistance in GC patients .
Conclusion : The exosomal transfer of macrophage-derived miR-223 conferred doxorubicin resistance in GC and targeting exosome communication may be a promising new therapeutic strategy for GC patients .

Purpose: Macrophages are a major component of the tumour microenvironment and play an important role in chemoresistance of cancer. However, how exosomal microRNAs (miRNAs) derived from macrophages contribute to the development of doxorubicin resistance in gastric cancer (GC) are not clearly defined. The aim of this study was to investigate whether macrophage-derived exosomes mediate doxorubicin resistance in GC.
Methods: Exosomes isolated from macrophage culture medium were characterized and co-cultured with GC cells and the miR-223 level was detected using real-time quantitative PCR (RT-qPCR). The internalization of exosomes and transfer of miR-223 were observed via immunofluorescence. Macrophages were transfected with an miR-223 inhibitor or negative control. Cell Counting Kit-8 and flow cytometry were employed to explore the effect of macrophage-derived exosomes on the doxorubicin resistance of GC cells. Western blot and RT-qPCR assay were also performed to explore the regulation of GC chemotherapy resistance by exosomal miR-223.
Results: Here, the macrophages and macrophage-derived exosomes promoted doxorubicin resistance in GC cells. MiR-223 was enriched in macrophage-derived exosomes and they could be transferred to co-cultivated GC cells. The miR-223 knockdown in macrophages could reduce the effects of exosomes on GC cells. Functional studies revealed that exosomal miR-223 derived from macrophages promoted doxorubicin resistance in GC cells by inhibiting F-box and WD repeat domain-containing 7 (). Clinically, the expression of miR-223 significantly increased in GC tissues and high expression of plasma exosomal miR-223 was highly linked with doxorubicin resistance in GC patients.
Conclusion: The exosomal transfer of macrophage-derived miR-223 conferred doxorubicin resistance in GC and targeting exosome communication may be a promising new therapeutic strategy for GC patients.


greenmedinfo--2020-12-19--The present study provides confirmation that exosomal miR-125a-5p could potentially serve as a bioma

Exosomal microRNAs ( miRs/miRNAs ) have been reported to be associated with cervical cancer .
The aim of the present study was to investigate circulating exosomal miRNA as a biomarker for cervical cancer diagnosis .
In the present study , samples from 6 patients with cervical cancer and 6 healthy control subjects were retrieved for exosomal RNA-sequencing .
The results revealed that a total of 39 miRNAs were differentially expressed between patients with cervical cancer and healthy controls ( P < 0.001 ; fold-change > 2.0 ) .
Exosomal miR-125a-5p was further quantified in plasma from 60 subjects , which @ @ @ @ @ @ @ with cervical cancer .
miR-16a-5p served as the reference miRNA for quantitative PCR analysis of exosomal miR-125a-5p in patients with cervical cancer and healthy individuals .
The results revealed that exosomal miR-125a-5p expression levels in the patients with cervical cancer were significantly lower than those in the healthy controls ( P < 0.001 ) .
Receiver operating characteristic ( ROC ) curve analyses were performed and the results revealed that the level of plasma exosomal miR-125a-5p was a potential marker for differentiating between non-cervical cancer and cervical cancer , with an ROC area @ @ @ @ @ @ @ the cut-off value of 2.537 for miR-125a-5p , cervical cancer diagnostic sensitivities and specificities were 59.1 and 84.2 % , respectively .
The present study provides confirmation that exosomal miR-125a-5p could potentially serve as a biomarker for cervical cancer diagnosis .
The present study involved only a small number of clinical samples ; more samples are required to support the conclusions of the present study .

Exosomal microRNAs (miRs/miRNAs) have been reported to be associated with cervical cancer. The aim of the present study was to investigate circulating exosomal miRNA as a biomarker for cervical cancer diagnosis. In the present study, samples from 6 patients with cervical cancer and 6 healthy control subjects were retrieved for exosomal RNA-sequencing. The results revealed that a total of 39 miRNAs were differentially expressed between patients with cervical cancer and healthy controls (P<0.001; fold-change>2.0). Exosomal miR-125a-5p was further quantified in plasma from 60 subjects, which included 22 healthy individuals and 38 patients with cervical cancer. miR-16a-5p served as the reference miRNA for quantitative PCR analysis of exosomal miR-125a-5p in patients with cervical cancer and healthy individuals. The results revealed that exosomal miR-125a-5p expression levels in the patients with cervical cancer were significantly lower than those in the healthy controls (P<0.001). Receiver operating characteristic (ROC) curve analyses were performed and the results revealed that the level of plasma exosomal miR-125a-5p was a potential marker for differentiating between non-cervical cancer and cervical cancer, with an ROC area under the curve of 0.7129. At the cut-off value of 2.537 for miR-125a-5p, cervical cancer diagnostic sensitivities and specificities were 59.1 and 84.2%, respectively. The present study provides confirmation that exosomal miR-125a-5p could potentially serve as a biomarker for cervical cancer diagnosis. The present study involved only a small number of clinical samples; more samples are required to support the conclusions of the present study.


greenmedinfo--2020-12-19--The role of cardiac exosomes in myocardial repair at the glance.

Exosome-based therapy is an emerging novel approach for myocardial infarction ( MI ) treatment .
Exosomes are identified as extracellular vesicles that are produced within multi vesicular bodies in the cells cytosols and then are secreted from the cells .
Exosomes are 30-100 nm in diameter that are released from viable cells and are different from other secreted vesicles such as apoptotic bodies and microvesicles in their origin and contents such as RNAs , proteins and nucleic acid .
The recent advances in exosomes researches have demonstrated the role of these bio-nanovesicles in the physiolocal , pathological and molecular aspects @ @ @ @ @ @ @ In vitro and preclinical models have shown that exosmes from different cardiac cells can improve the cardiac function following MI .
For example , mesenchymal stem cells ( MSCs ) and cardiac progenitor cells ( CPCs ) containing exosomes can affect proliferation , survival and differentiation of cardiac fibroblasts and cardiomyocytes .
Moreover , MSCs and CPCs- derived exosomes can enhance the migration of endothelial cells .
Exosome-based therapy approaches augment the cardiac function by multiple means , such as reducing fibrosis , stimulation of vascular angiogenesis and proliferation of cardiomyocytes that result @ @ @ @ @ @ @ generated functionall myocytes .
This review article aims to briefly discuss the recent advancements in the role of secreted exosomes in myocardial repair , by focusing on cardiac cells- derived exosomes .
This article is protected by copyright .
All rights reserved .

Exosome-based therapy is an emerging novel approach for myocardial infarction (MI) treatment. Exosomes are identified as extracellular vesicles that are produced within multi vesicular bodies in the cells cytosols and then are secreted from the cells. Exosomes are 30-100 nm in diameter that are released from viable cells and are different from other secreted vesicles such as apoptotic bodies and microvesicles in their origin and contents such as RNAs, proteins and nucleic acid. The recent advances in exosomes researches have demonstrated the role of these bio-nanovesicles in the physiolocal, pathological and molecular aspects of the heart. The results of In vitro and preclinical models have shown that exosmes from different cardiac cells can improve the cardiac function following MI. For example, mesenchymal stem cells (MSCs) and cardiac progenitor cells(CPCs) containing exosomes can affect proliferation, survival and differentiation of cardiac fibroblasts and cardiomyocytes. Moreover, MSCs and CPCs- derived exosomes can enhance the migration of endothelial cells. Exosome-based therapy approaches augment the cardiac function by multiple means, such as reducing fibrosis, stimulation of vascular angiogenesis and proliferation of cardiomyocytes that result in replacing damaged heart tissue with newly generated functionall myocytes. This review article aims to briefly discuss the recent advancements in the role of secreted exosomes in myocardial repair, by focusing on cardiac cells- derived exosomes. This article is protected by copyright. All rights reserved.


greenmedinfo--2020-12-19--Blood exosomes have neuroprotective effects in a mouse model of Parkinson's disease.

Parkinson 's disease ( PD ) is a common and complex neurodegenerative disease ; the pathogenesis of which is still uncertain .
Exosomes , nanosized extracellular vesicles , have been suggested to participate in the pathogenesis of PD , but their role is unknown .
Here , a metabolomic analysis of serum and brain exosomes showed differentially expressed metabolites between 1-Methyl-4-phenyl-1 , 2 , 3 , 6-tetrahydropyridine hydrochloride- ( MPTP- ) induced PD mice and control mice , such as oxidized lipids , vitamins , and cholesterol .
These metabolites were enriched in coenzyme , nicotinamide , and amino acid @ @ @ @ @ @ @ could be served as preclinical biomarkers .
We further found that blood-derived exosomes from healthy volunteers alleviated impaired motor coordination in MPTP-treated mice .
Results from immunohistochemistry and western blotting indicated that the loss of dopaminergic neurons in substantia nigra and striatum of PD model mice was rescued by the exosome treatment .
The exosome treatment also restored the homeostasis of oxidative stress , neuroinflammation , and cell apoptosis in the model mice .
These results suggest that exosomes are important mediators for PD pathogenesis , and exosomes are promising targets for the @ @ @ @ @ @

Parkinson's disease (PD) is a common and complex neurodegenerative disease; the pathogenesis of which is still uncertain. Exosomes, nanosized extracellular vesicles, have been suggested to participate in the pathogenesis of PD, but their role is unknown. Here, a metabolomic analysis of serum and brain exosomes showed differentially expressed metabolites between 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine hydrochloride- (MPTP-) induced PD mice and control mice, such as oxidized lipids, vitamins, and cholesterol. These metabolites were enriched in coenzyme, nicotinamide, and amino acid pathways related to PD, and they could be served as preclinical biomarkers. We further found that blood-derived exosomes from healthy volunteers alleviated impaired motor coordination in MPTP-treated mice. Results from immunohistochemistry and western blotting indicated that the loss of dopaminergic neurons in substantia nigra and striatum of PD model mice was rescued by the exosome treatment. The exosome treatment also restored the homeostasis of oxidative stress, neuroinflammation, and cell apoptosis in the model mice. These results suggest that exosomes are important mediators for PD pathogenesis, and exosomes are promising targets for the diagnosis and treatment of PD.


greenmedinfo--2020-12-19--Melatonin-stimulated exosomes originating from adipose-derived MSCs are safe and efficient tools for

Melatonin-stimulated exosomes originating from adipose-derived MSCs are safe and efficient tools for regenerative medicine to treat inflammatory diseases.

The positive effects of mesenchymal stem cells ( MSCs ) are primarily activated through molecular secretions known as paracrine activity @ @ @ @ @ of various cell types including immune cells .
Accumulating evidence shows that exosomes of soluble @ @ @ @ @ potential alternative agents for stem cell-based therapy , although the exact underlying mechanism has not @ @ @ @ @ of this study was to evaluate the potential effects of exosomes produced by adipose-derived MSCs @ @ @ @ @ in anti-inflammatory genes in concurrence with the polarization of M2 macrophages in cellular models ex @ @ @ @ @ used to investigate the inflammatory modulation in pro-inflammatory cytokine-treated fibroblasts and THP-1 cells .
The @ @ @ @ @ M2 macrophages was significantly upregulated after exosome treatment in an interferon gamma and tumor necrosis @ @ @ @ @ Furthermore , melatonin-stimulated exosomes exerted superior anti-inflammatory modulation via exosomal miRNAs miR-34a , miR-124 , @ @ @ @ @ exosomes .
Our results indicate that melatonin-stimulated exosomes originating from adipose-derived MSCs are safe and @ @ @ @ @ to treat inflammatory diseases .

The positive effects of mesenchymal stem cells (MSCs) are primarily activated through molecular secretions known as paracrine activity, which regulates the function of various cell types including immune cells. Accumulating evidence shows that exosomes of soluble factors released from MSCs are potential alternative agents for stem cell-based therapy, although the exact underlying mechanism has not been elucidated. The purpose of this study was to evaluate the potential effects of exosomes produced by adipose-derived MSCs and to examine the changes in anti-inflammatory genes in concurrence with the polarization of M2 macrophages in cellular models ex vivo. Isolated exosomes were used to investigate the inflammatory modulation in pro-inflammatory cytokine-treated fibroblasts and THP-1 cells. The anti-inflammatory mRNA expression associated with M2 macrophages was significantly upregulated after exosome treatment in an interferon gamma and tumor necrosis factor alpha-treated inflammatory environment. Furthermore, melatonin-stimulated exosomes exerted superior anti-inflammatory modulation via exosomal miRNAs miR-34a, miR-124, and miR-135b, compared with exosomes. Our results indicate that melatonin-stimulated exosomes originating from adipose-derived MSCs are safe and efficient tools for regenerative medicine to treat inflammatory diseases.


greenmedinfo--2020-12-19--The role of tumor-isolated exosomes on suppression of immune reactions and cancer progression.

Exosomes are extracellular cells ( EVs ) emancipated by various cell types and are involved in cell-to-cell transmission .
In @ @ @ @ @ as local and systemic cells to cell mediators of oncogenic information and play a significant @ @ @ @ @ cancer through the horizontal transfer of various molecules , such as proteins and miRNAs.In this @ @ @ @ @ PubMed , MEDLINE , Science Direct , Cochrane , EMBASE , and Scopus were used @ @ @ @ @ of cancer cell-derived exosomes in tumor tissue is an important factor in detecting their role @ @ @ @ @ the other hand , a limited number of studies have examined the biodistribution of exosomes @ @ @ @ @ exosomes function as cancer biomarkers and support cancer treatment , we have a long way @ @ @ @ @ of exosomes and develop exosome-based cancer diagnostic and therapeutic strategies.This review describes the science and @ @ @ @ @ exosomes relative to cancer treatment resistance .

Exosomes are extracellular cells (EVs) emancipated by various cell types and are involved in cell-to-cell transmission. In cancer diseases, exosomes emerge as local and systemic cells to cell mediators of oncogenic information and play a significant role in the advancement of cancer through the horizontal transfer of various molecules, such as proteins and miRNAs.In this study, 66 articles from PubMed, MEDLINE, Science Direct, Cochrane, EMBASE, and Scopus were used as English sources.The biological distribution of cancer cell-derived exosomes in tumor tissue is an important factor in detecting their role in tumor increase; on the other hand, a limited number of studies have examined the biodistribution of exosomes in tumor tissues. While exosomes function as cancer biomarkers and support cancer treatment, we have a long way to improve the antitumor treatment of exosomes and develop exosome-based cancer diagnostic and therapeutic strategies.This review describes the science and significance of cancer pathogenesis and exosomes relative to cancer treatment resistance.


greenmedinfo--2020-12-19--The emerging role of exosomes in the pathogenesis, prognosis and treatment of necrotizing enterocoli

The emerging role of exosomes in the pathogenesis, prognosis and treatment of necrotizing enterocolitis.

Exosomes are a subtype of extracellular vesicles .
They contain bioactive molecules , including nucleic acids , proteins and lipids @ @ @ @ @ exosomes , a majority are potential candidates for the diagnosis and treatment of necrotizing enterocolitis @ @ @ @ @ this work , we reviewed existing literature reports on exosomes and explored their roles in @ @ @ @ @ intestinal epithelial cells ( IECs ) participates in the development of intestinal diseases , thus @ @ @ @ @ biomarkers for NEC .
Besides , exosomes of human milk have been demonstrated to protect @ @ @ @ @ stimulate intestinal stem cells activity , improve the proliferation and migration of IECs , and @ @ @ @ @ of experimental NEC .
Further , exosomes produced by stem cells can reduce the severity @ @ @ @ @ the intestinal barrier function during NEC .
Conclusively , exosomes have been shown to influence @ @ @ @ @ exert a protective effect on NEC .
However , additional investigations would be urgently necessary @ @ @ @ @ mechanisms of exosomes in NEC .

Exosomes are a subtype of extracellular vesicles. They contain bioactive molecules, including nucleic acids, proteins and lipids. Among the currently described exosomes, a majority are potential candidates for the diagnosis and treatment of necrotizing enterocolitis (NEC). In this work, we reviewed existing literature reports on exosomes and explored their roles in NEC. Exosomes derived from intestinal epithelial cells (IECs) participates in the development of intestinal diseases, thus can potentially be utilized as biomarkers for NEC. Besides, exosomes of human milk have been demonstrated to protect IECs from oxidative stress, stimulate intestinal stem cells activity, improve the proliferation and migration of IECs, and lower the incidence and severity of experimental NEC. Further, exosomes produced by stem cells can reduce the severity of experimental NEC and protect the intestinal barrier function during NEC. Conclusively, exosomes have been shown to influence the pathogenesis of NEC and exert a protective effect on NEC. However, additional investigations would be urgently necessary to comprehensively elucidate the underlying mechanisms of exosomes in NEC.


greenmedinfo--2020-12-19--Growing evidence of exosomal microRNA-related metastasis of hepatocellular carcinoma.

Metastasis is the prominent cause of death in patients with hepatocellular carcinoma ( HCC ) ; however , the mechanisms @ @ @ @ @ well understood .
MicroRNAs ( miRs ) can regulate gene expression and affect HCC metastasis @ @ @ @ @ and other cargoes to and from different cells , thus being associated with tumour-distant metastasis @ @ @ @ @ processes of HCC metastasis through their functional effects , such as their induction of epithelial-to-mesenchymal @ @ @ @ @ distant niche .
In this review , data from the literature were analysed and summarised @ @ @ @ @ the evidence extraction of exosomal miRs in HCC metastasis with the purpose of increasing the @ @ @ @ @ HCC metastasis and acquiring implications for application .

Metastasis is the prominent cause of death in patients with hepatocellular carcinoma (HCC); however, the mechanisms behind HCC metastasis are not well understood. MicroRNAs (miRs) can regulate gene expression and affect HCC metastasis. Exosomes can transport miRs and other cargoes to and from different cells, thus being associated with tumour-distant metastasis. Exosomal miRs involve different processes of HCC metastasis through their functional effects, such as their induction of epithelial-to-mesenchymal transition, angiogenesis, and distant niche. In this review, data from the literature were analysed and summarised, with a focus on the evidence extraction of exosomal miRs in HCC metastasis with the purpose of increasing the understanding of the mechanisms behind HCC metastasis and acquiring implications for application.


greenmedinfo--2020-12-19--Stem cell-derived exosomes ameliorate doxorubicin-induced muscle toxicity through counteracting pyro

Stem cell-derived exosomes ameliorate doxorubicin-induced muscle toxicity through counteracting pyroptosis.

Doxorubicin ( Dox ) -induced muscle toxicity ( DIMT ) is a common occurrence in cancer patients ; however , the cause of its development and progression is not established .
We tested whether inflammation-triggered cell death , '' pyroptosis '' plays a role in DIMT .
We also examined the potential role of exosomes derived from embryonic stem cells ( ES-Exos ) in attenuating DIMT .
C57BL/6J mice ( 10± 2 wks age ) underwent the following treatments : Control ( saline ) , Dox , Dox+ES-Exos , and Dox+MEF-Exos ( mouse-embryonic fibroblast-derived exosomes , negative control ) .
@ @ @ @ @ @ @ muscle function in mice , which was associated with a significant increase inNLRP3 inflammasome and initiation marker TLR4 as compared with controls .
Pyroptosis activator , ASC , was significantly increased compared to controls with an upregulation of specific markers ( caspase-1 , IL-1β , and IL-18 ) .
Treatment with ES-Exos but not MEF-Exos showed a significant reduction in inflammasome and pyroptosis along with improved muscle function .
Additionally , we detected a significant increase in pro-inflammatory cytokines ( TNF-α and IL-6 ) and inflammatory M1 macrophages in Dox-treated animals .
Treatment @ @ @ @ @ @ @ anti-inflammatory M2macrophages .
Furthermore , ES-Exos showed a significant reduction in muscular atrophy and fibrosis .
In conclusion , these results suggest that DIMT is mediated through inflammation and pyroptosis , which is attenuated following treatment with ES-Exos .

Doxorubicin (Dox)-induced muscle toxicity (DIMT) is a common occurrence in cancer patients; however, the cause of its development and progression is not established. We tested whether inflammation-triggered cell death,"pyroptosis"plays a role in DIMT. We also examined the potential role of exosomes derived from embryonic stem cells (ES-Exos) in attenuating DIMT. C57BL/6J mice (10± 2 wks age) underwent the following treatments: Control (saline), Dox, Dox+ES-Exos, and Dox+MEF-Exos (mouse-embryonic fibroblast-derived exosomes, negative control). Our results demonstrated that Dox significantly reduced muscle function in mice, which was associated with a significant increase inNLRP3 inflammasome and initiation marker TLR4 as compared with controls. Pyroptosis activator, ASC, was significantly increased compared to controls with an upregulation of specific markers (caspase-1, IL-1β, and IL-18). Treatment with ES-Exos but not MEF-Exos showed a significant reduction in inflammasome and pyroptosis along with improved muscle function. Additionally, we detected a significant increase in pro-inflammatory cytokines (TNF-α and IL-6) and inflammatory M1 macrophages in Dox-treated animals. Treatment with ES-Exos decreased M1 macrophages and upregulated anti-inflammatory M2macrophages. Furthermore, ES-Exos showed a significant reduction in muscular atrophy and fibrosis. In conclusion, these results suggest that DIMT is mediated through inflammation and pyroptosis, which is attenuated following treatment with ES-Exos.


greenmedinfo--2020-12-19--The role of exosomes in the female reproductive system and breast cancers.

Exosomes are nanoscale extracellular vesicles released by nearly all cell types .
Exosomes were originally considered as waste receptacles for @ @ @ @ @ however , these organelles are now considered to be important for cell communication by delivering @ @ @ @ @ proteins , DNA , non-coding RNA and mRNA .
Studies have revealed that exosomes are @ @ @ @ @ , especially cancers .
Exosomes are indispensable for the emergence and progression of tumor .
@ @ @ @ @ status of research on exosomes in the female reproductive system cancers and breast cancer , @ @ @ @ @ in chemical resistance and immune responses , as well as their underlying applications in drug @ @ @ @ @ biological markers for tumor diagnosis .

Exosomes are nanoscale extracellular vesicles released by nearly all cell types. Exosomes were originally considered as waste receptacles for discarding unwanted cellular products; however, these organelles are now considered to be important for cell communication by delivering biologically active molecules such as proteins, DNA, non-coding RNA and mRNA. Studies have revealed that exosomes are closely related to several diseases, especially cancers. Exosomes are indispensable for the emergence and progression of tumor. Here, we review the status of research on exosomes in the female reproductive system cancers and breast cancer, focusing on their biological roles in chemical resistance and immune responses, as well as their underlying applications in drug delivery and nanotherapy and as biological markers for tumor diagnosis.


greenmedinfo--2020-12-19--Cisplatin-resistant osteosarcoma cell-derived exosomes confer cisplatin resistance to recipient cell

Cisplatin-resistant osteosarcoma cell-derived exosomes confer cisplatin resistance to recipient cells.

Studies have shown that exosomes can mediate the chemoresistance of drug-resistant cells by transmitting circular RNAs ( circRNAs ) .
However , the role of exosome-derived hsa_circ_103801 ( exosomal hsa_circ_103801 ) in osteosarcoma ( OS ) remains unclear .
The level of hsa_circ_103801 was upregulated in the serum exosomes from patients with OS , and OS patients with high hsa_circRNA_103801 expression had a shorter survival time relative to patients with low hsa_circ_103801 expression .
The expression of hsa_circ_103801 was upregulated in cisplatin-resistant MG63 ( MG63/CDDP ) cells compared to that in MG63 cells .
Additionally , hsa_circ_103801 was highly enriched @ @ @ @ @ @ @ and could be delivered to MG63 and U2OS cells through exosomes .
Exosomes derived from CDDP-resistant cells were shown to reduce the sensitivity of MG63 and U2OS cells to CDDP , inhibit apoptosis , and increase the expression of multidrug resistance-associated protein 1 and P-glycoprotein .
Moreover , exosomal hsa_circ_103801 could strengthen the promotive effect of exosomes on the chemoresistance of MG63 and U2OS cells to CDDP .
Hence , serum exosomal hsa_circ_103801 may serve as an effective prognostic biomarker for OS , and exosomal hsa_circ_103801 could be a potential target for overcoming @ @ @ @ @ @ @ by copyright .
All rights reserved .

Studies have shown that exosomes can mediate the chemoresistance of drug-resistant cells by transmitting circular RNAs (circRNAs). However, the role of exosome-derived hsa_circ_103801 (exosomal hsa_circ_103801) in osteosarcoma (OS) remains unclear. The level of hsa_circ_103801 was upregulated in the serum exosomes from patients with OS, and OS patients with high hsa_circRNA_103801 expression had a shorter survival time relative to patients with low hsa_circ_103801 expression. The expression of hsa_circ_103801 was upregulated in cisplatin-resistant MG63 (MG63/CDDP) cells compared to that in MG63 cells. Additionally, hsa_circ_103801 was highly enriched in exosomes derived from CDDP-resistant OS cells and could be delivered to MG63 and U2OS cells through exosomes. Exosomes derived from CDDP-resistant cells were shown to reduce the sensitivity of MG63 and U2OS cells to CDDP, inhibit apoptosis, and increase the expression of multidrug resistance-associated protein 1 and P-glycoprotein. Moreover, exosomal hsa_circ_103801 could strengthen the promotive effect of exosomes on the chemoresistance of MG63 and U2OS cells to CDDP. Hence, serum exosomal hsa_circ_103801 may serve as an effective prognostic biomarker for OS, and exosomal hsa_circ_103801 could be a potential target for overcoming OS chemoresistance. This article is protected by copyright. All rights reserved.


greenmedinfo--2020-12-19--Emerging roles of exosomes in type 1 diabetes mellitus.

Type 1 diabetes mellitus ( T1DM ) is a complex autoimmune disorder that mainly affects children and adolescents .
The elevated blood glucose level of patients with T1DM results from absolute insulin deficiency and leads to hyperglycemia and the development of life-threatening diabetic complications .
Although great efforts have been made to elucidate the pathogenesis of this disease , the precise underlying mechanisms are still obscure .
Emerging evidence indicates that small extracellular vesicles , namely , exosomes , take part in intercellular communication and regulate interorgan crosstalk .
More importantly , many findings suggest that exosomes and their cargo @ @ @ @ @ @ @ .
Therefore , a deeper understanding of exosomes is beneficial for further elucidating the pathogenic process of T1DM .
Exosomes are promising biomarkers for evaluating the risk of developingty T1DM , monitoring the disease state and predicting related complications because their number and composition can reflect the status of their parent cells .
Additionally , since exosomes are natural carriers of functional proteins , RNA and DNA , they can be used as therapeutic tools to deliver these molecules and drugs .
In this review , we briefly introduce the current understanding of @ @ @ @ @ @ @ the relationship between exosomes and T1DM from three perspectives , i.e.
, the pathogenic role of exosomes in T1DM , exosomes as novel biomarkers of T1DM and exosomes as therapeutic tools for T1DM .

Type 1 diabetes mellitus (T1DM) is a complex autoimmune disorder that mainly affects children and adolescents. The elevated blood glucose level of patients with T1DM results from absolute insulin deficiency and leads to hyperglycemia and the development of life-threatening diabetic complications. Although great efforts have been made to elucidate the pathogenesis of this disease, the precise underlying mechanisms are still obscure. Emerging evidence indicates that small extracellular vesicles, namely, exosomes, take part in intercellular communication and regulate interorgan crosstalk. More importantly, many findings suggest that exosomes and their cargo are associated with the development of T1DM. Therefore, a deeper understanding of exosomes is beneficial for further elucidating the pathogenic process of T1DM. Exosomes are promising biomarkers for evaluating the risk of developingty T1DM, monitoring the disease state and predicting related complications because their number and composition can reflect the status of their parent cells. Additionally, since exosomes are natural carriers of functional proteins, RNA and DNA, they can be used as therapeutic tools to deliver these molecules and drugs. In this review, we briefly introduce the current understanding of exosomes. Next, we focus on the relationship between exosomes and T1DM from three perspectives, i.e., the pathogenic role of exosomes in T1DM, exosomes as novel biomarkers of T1DM and exosomes as therapeutic tools for T1DM.


greenmedinfo--2020-12-19--Grape seed proanthocyanidin extract may be an effective agent for the treatment of cognitive deficit

Grape seed proanthocyanidin extract may be an effective agent for the treatment of cognitive deficits associated with sporadic Alzheimer's disease.

Progressive memory loss and cognitive impairment are the main clinical manifestations of Alzheimer 's disease ( AD ) .
Currently , there is no effective drug available for the treatment of AD .
Previous studies have demonstrated that the cognitive impairment of AD is associated with oxidative stress and the inhibition of AKT and ERK phosphorylation .
Grape seed proanthocyanidin extract ( GSPE ) has been shown to have strong antioxidant effect and can protect the nervous system from oxidative stress damage .
This study aimed to investigate the protective effect of GSPE on the cognitive and synaptic impairments of @ @ @ @ @ @ @ induced by intracerebroventricular ( ICV ) injection of streptozotocin ( STZ ) ( ICV-STZ ) .
Rats were treated with GSPE ( 50 , 100 , or 200 mg/kg every day ) by intragastrical ( ig . )
administration for continuous 7 weeks , and ICV-STZ ( 3 mg/kg ) was performed on the first day and third day of week 5 .
Learning and memory abilities were assessed by the Morris water maze ( MWM ) test at week 8 .
After behavioral test , hippocampal long-term potentiation ( LTP ) was @ @ @ @ @ @ @ ( MDA ) , superoxide dismutases ( SOD ) , glutathione ( GSH ) and the protein expression of AKT and ERK were measured in the hippocampus and cerebral cortex of rats .
Our study revealed that ICV-STZ significantly impaired the working learning ability and hippocampal LTP of rats , significantly increased the levels of MDA , and decreased the activity of SOD and GSH in the hippocampus and cerebral cortex .
In contrast , GSPE treatment prevented the impairment of cognitive function and hippocampal LTP induced by ICV-STZ , decreased the level @ @ @ @ @ @ @ of SOD and GSH .
Furthermore , Western blot results showed that GSPE treatment could prevent the loss of AKT and ERK activities in the hippocampus and cerebral cortex induced by ICV-STZ .
Our findings demonstrate that GSPE treatment could ameliorate the impairment of cognitive ability and hippocampal synaptic plasticity in a rat model of sporadic AD by inhibiting oxidative stress and preserving AKT and ERK activities .
Therefore , GSPE may be an effective agent for the treatment of cognitive deficits associated with sporadic AD .

Progressive memory loss and cognitive impairment are the main clinical manifestations of Alzheimer's disease (AD). Currently, there is no effective drug available for the treatment of AD. Previous studies have demonstrated that the cognitive impairment of AD is associated with oxidative stress and the inhibition of AKT and ERK phosphorylation. Grape seed proanthocyanidin extract (GSPE) has been shown to have strong antioxidant effect and can protect the nervous system from oxidative stress damage. This study aimed to investigate the protective effect of GSPE on the cognitive and synaptic impairments of AD using a sporadic AD rat model induced by intracerebroventricular (ICV) injection of streptozotocin (STZ) (ICV-STZ). Rats were treated with GSPE (50, 100, or 200 mg/kg every day) by intragastrical (ig.) administration for continuous 7 weeks, and ICV-STZ (3 mg/kg) was performed on the first day and third day of week 5. Learning and memory abilities were assessed by the Morris water maze (MWM) test at week 8. After behavioral test, hippocampal long-term potentiation (LTP) was recorded, and the levels of malondialdehyde (MDA), superoxide dismutases (SOD), glutathione (GSH) and the protein expression of AKT and ERK were measured in the hippocampus and cerebral cortex of rats. Our study revealed that ICV-STZ significantly impaired the working learning ability and hippocampal LTP of rats, significantly increased the levels of MDA, and decreased the activity of SOD and GSH in the hippocampus and cerebral cortex. In contrast, GSPE treatment prevented the impairment of cognitive function and hippocampal LTP induced by ICV-STZ, decreased the level of MDA, and increased the level of SOD and GSH. Furthermore, Western blot results showed that GSPE treatment could prevent the loss of AKT and ERK activities in the hippocampus and cerebral cortex induced by ICV-STZ. Our findings demonstrate that GSPE treatment could ameliorate the impairment of cognitive ability and hippocampal synaptic plasticity in a rat model of sporadic AD by inhibiting oxidative stress and preserving AKT and ERK activities. Therefore, GSPE may be an effective agent for the treatment of cognitive deficits associated with sporadic AD.