Objective To investigate the effects of short-term forest bathing on human health. Methods Twenty healthy male university students participated as subjects and were randomly divided into two groups of 10. One group wa...Objective To investigate the effects of short-term forest bathing on human health. Methods Twenty healthy male university students participated as subjects and were randomly divided into two groups of 10. One group was sent on a two-night trip to a broad-leaved evergreen forest, and the other was sent to a city area. Serum cytokine levels reflecting inflammatory and stress response, indicators reflecting oxidative stress, the distribution of leukocyte subsets, and plasma endothelin-1 (ET-1) concentrations were measured before and after the experiment to evaluate the positive health effects of forest environments. A profile of mood states (POMS) evaluation was used to assess changes in mood states. Results No significant differences in the baseline values of the indicators were observed between the two groups before the experiment. Subjects exposed to the forest environment showed reduced oxidative stress and pro-inflammatory level, as evidenced by decreased malondialdehyde, interleukin-6, and tumor necrosis factor a levels compared with the urban group. Serum cortisol levels were also lower than in the urban group. Notably, the concentration of plasma ET-1 was much lower in subjects exposed to the forest environment. The POMS evaluation showed that after exposure to the forest environment, subjects had lower scores in the negative subscales, and the score for vigor was increased. Conclusion Forest bathing is beneficial to human health, perhaps through preventive effects related to several pathological factors.展开更多
Chronic heart failure (CHF), a clinical syndrome resulting from the consequences of various cardiovascular diseases (CVDs), is increasingly becoming a global cause of morbidity and mortality. We had earlier demons...Chronic heart failure (CHF), a clinical syndrome resulting from the consequences of various cardiovascular diseases (CVDs), is increasingly becoming a global cause of morbidity and mortality. We had earlier demonstrated that a 4-day forest bathing trip can provide an adjunctive therapeutic influence on patients with CHF. To further investigate the duration of the impact and the optimal frequency of forest bathing trips in patients with CHF, we recruited those subjects who had experienced the first forest bathing trip again after 4 weeks and randomly categorized them into two groups, namely, the urban control group (city) and the forest bathing group (forest). After a second 4-day forest bathing trip, we observed a steady decline in the brain natriuretic peptide levels, a biomarker of heart failure, and an attenuated inflammatory response as well as oxidative stress. Thus, this exploratory study demonstrated the additive benefits of twice forest bathing trips in elderly patients with CHF, which could further pave the way for analyzing the effects of such interventions in CVDs.展开更多
In recent years,due to regional pollution and deteriorating environment,combined with intense social competition and heavier life pressure,an increasing number of people are affected by lifestyle-related diseases and ...In recent years,due to regional pollution and deteriorating environment,combined with intense social competition and heavier life pressure,an increasing number of people are affected by lifestyle-related diseases and remain in a state of being sub-healthy.Therefore,health issue has been receiving unprecedented attention.展开更多
Salidroside(SAL) is a glucoside of tyrosol and a key constituent of Rhodiola rosea L. The diverse pharmacological activities of SAL include anti-inflammatory, cardioprotective, and neuroprotective effects(1)Our previo...Salidroside(SAL) is a glucoside of tyrosol and a key constituent of Rhodiola rosea L. The diverse pharmacological activities of SAL include anti-inflammatory, cardioprotective, and neuroprotective effects(1)Our previous investigation showed that the anti-aging effects of SAL involve reductions of the levels of advanced glycation end products in a D-galactose induced mouse model(2)Additionally.展开更多
Pyropia haitanensis polysaccharide(LP)have been found for having many excellent functions such as anti-aging.Using Caenorhabditis elegans models,we evaluated the anti-aging activity of LP by observing the lifespan,rep...Pyropia haitanensis polysaccharide(LP)have been found for having many excellent functions such as anti-aging.Using Caenorhabditis elegans models,we evaluated the anti-aging activity of LP by observing the lifespan,reproduction,pharyngeal pumping,stress response,quantitative fluorescence of polyglutamic acid,and nuclear localization of DAF-16 of worms.The results reveal that LP could extend the adult lifespan of wild-type and polyQ nematodes,indicating a connection of its anti-aging benefit with the toxicity-suppressing effect.The number of polyglutamic acid aggregates in high concentration groups decreased by 24.39%(P<0.05)to the control.The high-dose group strongly induced DAF-16 nuclear translocation over intermediate and cytosolic localizations compared with the control(P<0.001).Therefore,we believe that LP could extend the lifespan and reduce the protein aggregation in C.elegans through nuclear DAF-16∷GFP expression.展开更多
Eukaryotic organisms constantly face a wide range of internal and external factors that cause damage to their DNA.Failure to accurately and efficiently repair these DNA lesions can result in genomic instability and th...Eukaryotic organisms constantly face a wide range of internal and external factors that cause damage to their DNA.Failure to accurately and efficiently repair these DNA lesions can result in genomic instability and the development of tumors(Canela et al.,2017).Among the various forms of DNA damage,DNA doublestrand breaks(DSBs)are particularly harmful.Two major pathways,non-homologous end joining(NHEJ)and homologous recombination(HR),are primarily responsible for repairing DSBs(Katsuki et al.,2020;Li and Yuan,2021;Zhang and Gong,2021;Xiang et al.,2023).NHEJ is an error-prone repair mechanism that simply joins the broken ends together(Blunt et al.,1995;Hartley et al.,1995).展开更多
Programmed cell death-1(PD-1)/programmed cell death ligand-1(PD-L1)blocking therapy has become a major pillar of cancer immunotherapy.Compared with antibodies targeting,small-molecule checkpoint inhibitors which have ...Programmed cell death-1(PD-1)/programmed cell death ligand-1(PD-L1)blocking therapy has become a major pillar of cancer immunotherapy.Compared with antibodies targeting,small-molecule checkpoint inhibitors which have favorable pharmacokinetics are urgently needed.Here we identified berberine(BBR),a proven anti-inflammation drug,as a negative regulator of PDL1 from a set of traditional Chinese medicine(TCM)chemical monomers.BBR enhanced the sensitivity of tumour cells to co-cultured T-cells by decreasing the level of PD-L1 in cancer cells.In addition,BBR exerted its antitumor effect in Lewis tumor xenograft mice through enhancing tumorinfiltrating T-cell immunity and attenuating the activation of immunosuppressive myeloid-derived suppressor cells(MDSCs)and regulatory T-cells(Tregs).BBR triggered PD-L1 degradation through ubiquitin(Ub)/proteasome-dependent pathway.Remarkably,BBR selectively bound to the glutamic acid76 of constitutive photomorphogenic-9 signalosome 5(CSN5)and inhibited PD-1/PD-L1 axis through its deubiquitination activity,resulting in ubiquitination and degradation of PD-L1.Our data reveals a previously unrecognized antitumor mechanism of BBR,suggesting BBR is small-molecule immune checkpoint inhibitor for cancer treatment.展开更多
Pyroptosis is a form of programmed cell death mediated by gasdermin and is a product of continuous cell expansion until the cytomembrane ruptures,resulting in the release of cellular contents that can activate strong ...Pyroptosis is a form of programmed cell death mediated by gasdermin and is a product of continuous cell expansion until the cytomembrane ruptures,resulting in the release of cellular contents that can activate strong inflammatory and immune responses.Pyroptosis,an innate immune response,can be triggered by the activation of inflammasomes by various influencing factors.Activation of these inflammasomes can induce the maturation of caspase-1 or caspase-4/5/11,both of which cleave gasdermin D to release its N-terminal domain,which can bind membrane lipids and perforate the cell membrane.Here,we review the latest advancements in research on the mechanisms of pyroptosis,newly discovered influencing factors,antitumoral properties,and applications in various diseases.Moreover,this review also provides updates on potential targeted therapies for inflammation and cancers,methods for clinical prevention,and finally challenges and future directions in the field.展开更多
Programmed cell death ligand 1(PD-L1)/programmed cell death protein 1(PD-1)cascade is an effective therapeutic target for immune checkpoint blockade(ICB)therapy.Targeting PD-L1/PD-1 axis by small-molecule drug is an a...Programmed cell death ligand 1(PD-L1)/programmed cell death protein 1(PD-1)cascade is an effective therapeutic target for immune checkpoint blockade(ICB)therapy.Targeting PD-L1/PD-1 axis by small-molecule drug is an attractive approach to enhance antitumor immunity.Using flow cytometry-based assay,we identify tubeimoside-1(TBM-1)as a promising antitumor immune modulator that negatively regulates PD-L1 level.TBM-1 disrupts PD-1/PD-L1 interaction and enhances the cytotoxicity of T cells toward cancer cells through decreasing the abundance of PD-L1.Furthermore,TBM-1 exerts its antitumor effect in mice bearing Lewis lung carcinoma(LLC)and B16 melanoma tumor xenograft via activating tumor-infiltrating T-cell immunity.Mechanistically,TBM-1 triggers PD-L1 lysosomal degradation in a TFEB-dependent,autophagy-independent pathway.TBM-1 selectively binds to the mammalian target of rapamycin(m TOR)kinase and suppresses the activation of m TORC1,leading to the nuclear translocation of TFEB and lysosome biogenesis.Moreover,the combination of TBM-1 and anti-CTLA-4 effectively enhances antitumor T-cell immunity and reduces immunosuppressive infiltration of myeloid-derived suppressor cells(MDSCs)and regulatory T(Treg)cells.Our findings reveal a previously unrecognized antitumor mechanism of TBM-1 and represent an alternative ICB therapeutic strategy to enhance the efficacy of cancer immunotherapy.展开更多
基金supported by the project "Modern forestry-exploitation and utilization of therapeutic forest" commissioned by the Forestry Department of Zhejiang Provincefunds from the Ministry of Health of P.R.China (WKJ2011-2-014)+1 种基金the Science and Technology Department of Zhejiang Province Program (2008C33046)Zhejiang Provincial key disciplinary fields of Geriatrics Program (2007ZB006 and 2008ZJ004)
文摘Objective To investigate the effects of short-term forest bathing on human health. Methods Twenty healthy male university students participated as subjects and were randomly divided into two groups of 10. One group was sent on a two-night trip to a broad-leaved evergreen forest, and the other was sent to a city area. Serum cytokine levels reflecting inflammatory and stress response, indicators reflecting oxidative stress, the distribution of leukocyte subsets, and plasma endothelin-1 (ET-1) concentrations were measured before and after the experiment to evaluate the positive health effects of forest environments. A profile of mood states (POMS) evaluation was used to assess changes in mood states. Results No significant differences in the baseline values of the indicators were observed between the two groups before the experiment. Subjects exposed to the forest environment showed reduced oxidative stress and pro-inflammatory level, as evidenced by decreased malondialdehyde, interleukin-6, and tumor necrosis factor a levels compared with the urban group. Serum cortisol levels were also lower than in the urban group. Notably, the concentration of plasma ET-1 was much lower in subjects exposed to the forest environment. The POMS evaluation showed that after exposure to the forest environment, subjects had lower scores in the negative subscales, and the score for vigor was increased. Conclusion Forest bathing is beneficial to human health, perhaps through preventive effects related to several pathological factors.
基金supported by funds from the National Natural Science Foundation of China[31670701&81771520]the Science Technology Department of Zhejiang Province[2014C33130&2016C34002]+1 种基金the Natural Science Foundation of Zhejiang Province[Y15H050018&LY17C070004]the Health Bureau of Zhejiang Province[2015DTA001&2016KYB005]
文摘Chronic heart failure (CHF), a clinical syndrome resulting from the consequences of various cardiovascular diseases (CVDs), is increasingly becoming a global cause of morbidity and mortality. We had earlier demonstrated that a 4-day forest bathing trip can provide an adjunctive therapeutic influence on patients with CHF. To further investigate the duration of the impact and the optimal frequency of forest bathing trips in patients with CHF, we recruited those subjects who had experienced the first forest bathing trip again after 4 weeks and randomly categorized them into two groups, namely, the urban control group (city) and the forest bathing group (forest). After a second 4-day forest bathing trip, we observed a steady decline in the brain natriuretic peptide levels, a biomarker of heart failure, and an attenuated inflammatory response as well as oxidative stress. Thus, this exploratory study demonstrated the additive benefits of twice forest bathing trips in elderly patients with CHF, which could further pave the way for analyzing the effects of such interventions in CVDs.
基金supported by funds from the National Natural Science Foundation of China[31670701]Health Bureau of Zhejiang Province[2016KYB005]
文摘In recent years,due to regional pollution and deteriorating environment,combined with intense social competition and heavier life pressure,an increasing number of people are affected by lifestyle-related diseases and remain in a state of being sub-healthy.Therefore,health issue has been receiving unprecedented attention.
基金supported by the National Natural Science Foundation of China [81771520 and 81501113]the Science Technology Department of Zhejiang Province [2016C34002]+2 种基金funds from the Natural Science Foundation of Zhejiang province [LQ16H020006]the Health Bureau of Zhejiang Province [2019KY257,2019RC091,2017KY189,2017KY188,2015DTA001,and 2015KYA001]Chinese traditional medicine science and technology projects of Zhejiang Province [2017ZB002,2015ZA002,and 2014ZB001]
文摘Salidroside(SAL) is a glucoside of tyrosol and a key constituent of Rhodiola rosea L. The diverse pharmacological activities of SAL include anti-inflammatory, cardioprotective, and neuroprotective effects(1)Our previous investigation showed that the anti-aging effects of SAL involve reductions of the levels of advanced glycation end products in a D-galactose induced mouse model(2)Additionally.
基金Supported by the National Natural Science Foundation of China(Nos.31700307,41876165)the Science and Technology Project of Huzhou(No.2017ZD2017)the Key Research Program of Frontier Sciences,Chinese Academy of Sciences(No.QYZDB-SSW-DQC023)。
文摘Pyropia haitanensis polysaccharide(LP)have been found for having many excellent functions such as anti-aging.Using Caenorhabditis elegans models,we evaluated the anti-aging activity of LP by observing the lifespan,reproduction,pharyngeal pumping,stress response,quantitative fluorescence of polyglutamic acid,and nuclear localization of DAF-16 of worms.The results reveal that LP could extend the adult lifespan of wild-type and polyQ nematodes,indicating a connection of its anti-aging benefit with the toxicity-suppressing effect.The number of polyglutamic acid aggregates in high concentration groups decreased by 24.39%(P<0.05)to the control.The high-dose group strongly induced DAF-16 nuclear translocation over intermediate and cytosolic localizations compared with the control(P<0.001).Therefore,we believe that LP could extend the lifespan and reduce the protein aggregation in C.elegans through nuclear DAF-16∷GFP expression.
基金supported by the National Key Research ar d Development Program of China(Nos.2022YFA 1302800 and 2021 YFA 1101000)the National Natural Science Foundation of China(Nos.31961160725,31730021,31971220,32270769,and 32170730)+4 种基金the Fok Ying Tung Education Foundation,the Fundamental Research Funds for the Provincial Universities of Zhejiang(No.2021XZZX039)the Natural Science Foundation of Shaanxi Province(No.2023-JC-QN-0942)the Research Fund of Xi'an Jiaotong University(No.YXJLRH2022098)the Research Fund of the Second A filiated Hospital of Xi an Jiaotong University(Nos.2020YJ(ZY TS)546-10Y J(QN)202014),China.
文摘Eukaryotic organisms constantly face a wide range of internal and external factors that cause damage to their DNA.Failure to accurately and efficiently repair these DNA lesions can result in genomic instability and the development of tumors(Canela et al.,2017).Among the various forms of DNA damage,DNA doublestrand breaks(DSBs)are particularly harmful.Two major pathways,non-homologous end joining(NHEJ)and homologous recombination(HR),are primarily responsible for repairing DSBs(Katsuki et al.,2020;Li and Yuan,2021;Zhang and Gong,2021;Xiang et al.,2023).NHEJ is an error-prone repair mechanism that simply joins the broken ends together(Blunt et al.,1995;Hartley et al.,1995).
基金supported by grants from National Natural Science Foundation of China(81973366,81773782 and 81903695)CAMS Innovation Fund for Medical Sciences(2016-12M-1-011,China)+2 种基金Open Project of State Key Laboratory of Bioactive Substance and Function of Natural Medicines(GTZK201908,China)National Mega-project for Innovative Drugs(2019ZX09721-001,China)Chinese Pharmaceutical Association-Yiling Pharmaceutical Innovation Fund for Biomedicine(GL-1-B04-20180366,China)
文摘Programmed cell death-1(PD-1)/programmed cell death ligand-1(PD-L1)blocking therapy has become a major pillar of cancer immunotherapy.Compared with antibodies targeting,small-molecule checkpoint inhibitors which have favorable pharmacokinetics are urgently needed.Here we identified berberine(BBR),a proven anti-inflammation drug,as a negative regulator of PDL1 from a set of traditional Chinese medicine(TCM)chemical monomers.BBR enhanced the sensitivity of tumour cells to co-cultured T-cells by decreasing the level of PD-L1 in cancer cells.In addition,BBR exerted its antitumor effect in Lewis tumor xenograft mice through enhancing tumorinfiltrating T-cell immunity and attenuating the activation of immunosuppressive myeloid-derived suppressor cells(MDSCs)and regulatory T-cells(Tregs).BBR triggered PD-L1 degradation through ubiquitin(Ub)/proteasome-dependent pathway.Remarkably,BBR selectively bound to the glutamic acid76 of constitutive photomorphogenic-9 signalosome 5(CSN5)and inhibited PD-1/PD-L1 axis through its deubiquitination activity,resulting in ubiquitination and degradation of PD-L1.Our data reveals a previously unrecognized antitumor mechanism of BBR,suggesting BBR is small-molecule immune checkpoint inhibitor for cancer treatment.
基金This work was supported by a special program from the National Key Research and Development Program of China(2021YFA1101000 to LZ)the Chinese National Natural Science Funds(U20A201376,U20A20393,and 31925013 to LZ,82041009,31871405,and 32125016 to FZ,92169122 and 31701232 to FX,32025011 to FW,31822031,31970664,31961160725 to JH and TL)+3 种基金the Science and Technology Plan Project of Suzhou(SYS2019020 to FX)the Jiangsu National Science Foundation(BK20180043 to FZ)Natural Science Foundation of Zhejiang Province(LZ19C070001 to FW)the Key Project of University Natural Science Foundation of Jiangsu Province(19KJA550003 to FZ).
文摘Pyroptosis is a form of programmed cell death mediated by gasdermin and is a product of continuous cell expansion until the cytomembrane ruptures,resulting in the release of cellular contents that can activate strong inflammatory and immune responses.Pyroptosis,an innate immune response,can be triggered by the activation of inflammasomes by various influencing factors.Activation of these inflammasomes can induce the maturation of caspase-1 or caspase-4/5/11,both of which cleave gasdermin D to release its N-terminal domain,which can bind membrane lipids and perforate the cell membrane.Here,we review the latest advancements in research on the mechanisms of pyroptosis,newly discovered influencing factors,antitumoral properties,and applications in various diseases.Moreover,this review also provides updates on potential targeted therapies for inflammation and cancers,methods for clinical prevention,and finally challenges and future directions in the field.
基金supported by grants from National Natural Science Foundation of China(81973366,81773782,81903695 and 82003792)CAMS Innovation Fund for Medical Sciences(2016I2M-1-011,China)+1 种基金National Mega-project for Innovative Drugs(2019ZX09721-001,China)Chinese Pharmaceutical Association-Yiling Pharmaceutical Innovation Fund for Biomedicine(GL-1-B04-20180366,China)。
文摘Programmed cell death ligand 1(PD-L1)/programmed cell death protein 1(PD-1)cascade is an effective therapeutic target for immune checkpoint blockade(ICB)therapy.Targeting PD-L1/PD-1 axis by small-molecule drug is an attractive approach to enhance antitumor immunity.Using flow cytometry-based assay,we identify tubeimoside-1(TBM-1)as a promising antitumor immune modulator that negatively regulates PD-L1 level.TBM-1 disrupts PD-1/PD-L1 interaction and enhances the cytotoxicity of T cells toward cancer cells through decreasing the abundance of PD-L1.Furthermore,TBM-1 exerts its antitumor effect in mice bearing Lewis lung carcinoma(LLC)and B16 melanoma tumor xenograft via activating tumor-infiltrating T-cell immunity.Mechanistically,TBM-1 triggers PD-L1 lysosomal degradation in a TFEB-dependent,autophagy-independent pathway.TBM-1 selectively binds to the mammalian target of rapamycin(m TOR)kinase and suppresses the activation of m TORC1,leading to the nuclear translocation of TFEB and lysosome biogenesis.Moreover,the combination of TBM-1 and anti-CTLA-4 effectively enhances antitumor T-cell immunity and reduces immunosuppressive infiltration of myeloid-derived suppressor cells(MDSCs)and regulatory T(Treg)cells.Our findings reveal a previously unrecognized antitumor mechanism of TBM-1 and represent an alternative ICB therapeutic strategy to enhance the efficacy of cancer immunotherapy.