Aim To investigate the effect of linarin on improving cognitive behavior of APP/PS1 mice,and to explore the therapeutic effect of linarin on A β deposi-tion and neuroinflammation and its correlation.Meth-ods APP/PS1 transgenic mice were randomly divid-ed into the model group,high-dose group,medium-dose group,low-dose group and positive control group.C57BL/6J mice were set as the normal group.Morris water maze was used to evaluate the learning and mem-ory abilities of mice.TUNEL staining was used to de-tect the apoptosis of neurons in the CA1 region of mice.IHC was used to detect the expression levels of Aβ42 and GFAP.Western blot was used to detect the expression levels of BACE1 and PS-1.Results Com-pared with the normal group,mice of the model group showed lower NCP,shorter target quadrant travel,less target quadrant residence time percentage(all P＜0.01),higher apoptosis rate of neurons in the CA1 re-gion(P＜0.01),significantly higher protein expres-sion levels of A β42 and GFAP(all P＜0.01),and significantly higher protein expression levels of BACE1 and PS-1(all P＜0.01).Compared with the model group,the medium-dose group,high-dose group and positive control group showed higher NCP,longer tar-get quadrant travel,more target quadrant residence time percentage(all P＜0.05),lower apoptosis rate of neurons in the CA1 region(P＜0.01),significantly lower protein expression levels of A β42 and GFAP(all P＜0.01),and significantly lower protein expression levels of BACE1 and PS-1(all P＜0.01).Conclu-sions Linarin can inhibit two key enzymes to reduce the decomposition of APP and the generation of A β42,thereby inhibiting the activation of astrocytes,allevia-ting neuroinflammation,improving the core pathologi-cal features of AD,and thus significantly improving learning and memory impairment in APP/PS1 mice.

AIM To investigate the effects of Rutong Ruanjian Tablets on angiogenesis in cancer tissues of rats with preneoplastic breast cancer(PBC).METHODS 60 female SD rats were randomly divided into a blank group of 10 rats and a model group of 50 rats for the establishment of the PBC models of Liver-Qi Stagnation and Blood Stasis Pattern with 9 weeks of oral administration of 7,12-dimethylbenz[a]anthracene(DMBA)and cervical ligation.After successful modeling,the rats were randomly divided into the model group,the tamoxifen group(3.2 mg/kg),the Rutong Ruanjian Tablets group(128 mg/kg),the 3,5-difluorobenzoyl group(DAPT,5 mg/kg),and the Rutong Ruanjian Tablets(128 mg/kg via gavage)+DAPT(5 mg/kg intraperitoneal injection)group,for 1 month corresponding drug administration,with 10 rats in each group.Then the rats had their cancer progression and syndrome scores observed;their angiogenesis evaluated by assessment of microvascular density(MVD);their vascular endothelial growth factor(VEGF)expression assessed by immunohistochemistry;and their mRNA and protein expressions of proteins related to the DLL4/Notch1/Hes1 pathway measured using RT-qPCR,immunohistochemistry and Western blot.RESULTS During carcinogenesis of rats induced by DMBA,there was gradual disappearance of E-cadherin expression and consistency of HE staining result with the PBC progression confirming the success of the modeling.Compared with the blank group,the model group showed increased MVD values,mRNA expression of Notch1 and Hes1,and protein expressions of VEGF,DLL4,Notch1 and Hes1(P＜0.05,P＜0.01).Compared with the model group,the Rutong Ruanjian Tablets group exhibited reduced MVD values,mRNA expression of Notch1 and Hes1,and protein expressions of VEGF,DLL4,Notch1 and Hes1(P＜0.05,P＜0.01).The Rutong Ruanjian Tablets+DAPT group showed reduced mRNA expression of Notch1 and Hes1,and protein expressions of DLL4,Notch1 and Hes1 compared to the Rutong Ruanjian Tablets group(P＜0.05,P＜0.01).CONCLUSION Rutong Ruanjian Tablets can inhibit angiogenesis and attenuate cancer progression in PBC rats of Liver-Qi Stagnation and Blood Stasis Pattern,and the mechanism may lie in the downregulation of DLL4/Notch1/Hes1 signaling pathway related proteins.

Aim To investigate the effects of endur-ance exercise(EE)on rats following cerebral ischemi-a/reperfusion injury(CI/RI)and to explore its rela-tionship with the Mas signaling pathway.Methods Seventy-two adult male SD rats were randomly divided into four groups(n=18 each):sham group,model group,EE group(group E),and A779 pretreatment group(group A).The CI/RI model was established u-sing middle cerebral artery occlusion method Rats in both group E and group A underwent regular running for four weeks before model preparation,while rats in group A were injected with A779 30 minutes before model preparation.The cognitive function of rats was evaluated using the Neurological Disability Score(NDS)and Morris water maze test.After intravenous injection of Evans blue(EB)for one hour,the rats were euthanized,and brain tissues were collected to measure the infarction volume,EB content,ROS con-tent,and the percentage of apoptotic neurons of the hippocampal CA1 region.The protein expression relat-ed to the Mas pathway was detected by Western blot.Results Compared with the model group,the learning and memory ability as well as the neurological function in group E exhibited a significant improvement(P＜0.05).Both the cerebral infarction volume and the ap-optotic neuron percentage in the ischemic hippocampal CA1 region showed a significant reduction in group E(P＜0.05).The ROS content along with the EB con-tent in the brain tissue significantly decreased in group E(P＜0.05).Furthermore,the expressions of Mas/PKA/CREB/UCP2 pathway related proteins were sig-nificantly enhanced in group E(P＜0.05).However,the Mas receptor antagonist A779 significantly inhibited these neurological effects(P＜0.05).Conclusion EE may inhibit oxidative stress and alleviate CI/RI in rats by activating the Mas/PKA/CREB/UCP2 signaling pathway.

Lung cancer poses a serious threat to global public health security.Chemotherapy,as the main strategy for cancer treatment,faces challenges such as high toxicity and drug resistance.Anticancer peptides have the potential of being developed into new anticancer drugs due to their advantages of broad-spectrum anticancer activity,rapid action,and difficulty in generating drug resistance,but they also face shortcomings such as weak activity and strong toxic side effects.The weakly acidic microenvironment of tumors(pH 6.5-6.8)provides a good idea for the design of anticancer peptides of high-efficiency and low-toxicity.Previously,we designed the acid-sensitive antibacterial peptide pHly-1 using the wolf spider(Lycosa singoriensis)toxin Lycosin-Ⅰ as a template.In this study,we found that pHly-1 also had acid-sensitive anticancer activity.Further alanine scanning analysis of pHly-1 was carried out,and we ob-tained a mutant pHTP-2 with better acid sensitivity,whose IC50(half maximal inhibitory concentration)against A549 cells was 15.68 μmol/L at pH 6.6 and was greater than 100 μmol/L at pH 7.4.At pH 6.6,pHTP-2 could act on various lung cancer cell lines and induce the death of A549 cells by rapid ly-sis;at pH 7.4,500 μmol/L pHTP-2 had weak toxicity to red blood cells(the hemolysis rate was ap-proximately 38％)and primary myocardial cells(the inhibition rate was 49.7％,with P＜0.05).Analy-sis of its charge,particle size,morphology,and secondary structure showed that at pH 6.6,the histidine in the sequence of pHTP-2 was protonated,increasing the positive charge(P＜0.01),decreasing the hy-drated particle size(P＜0.05)and forming an α-helical structure to induce membrane lysis of A549 cells.At pH 7.4,it was deprotonated,the positive charge decreases,a β-sheet structure was formed and self-aggregation occurred,limiting its effect on the A549 cell membrane and showing weak activity.In summary,pHTP-2 could respond to the weakly acidic microenvironment of tumors to exert selective cyto-toxic activity,effectively overcoming the shortcomings of anticancer peptides such as low efficiency and high toxicity.Our findings suggest that it is a high-quality lead molecule for anticancer drugs.

Lung cancer poses a serious threat to global public health security.Chemotherapy,as the main strategy for cancer treatment,faces challenges such as high toxicity and drug resistance.Anticancer peptides have the potential of being developed into new anticancer drugs due to their advantages of broad-spectrum anticancer activity,rapid action,and difficulty in generating drug resistance,but they also face shortcomings such as weak activity and strong toxic side effects.The weakly acidic microenvironment of tumors(pH 6.5-6.8)provides a good idea for the design of anticancer peptides of high-efficiency and low-toxicity.Previously,we designed the acid-sensitive antibacterial peptide pHly-1 using the wolf spider(Lycosa singoriensis)toxin Lycosin-Ⅰ as a template.In this study,we found that pHly-1 also had acid-sensitive anticancer activity.Further alanine scanning analysis of pHly-1 was carried out,and we ob-tained a mutant pHTP-2 with better acid sensitivity,whose IC50(half maximal inhibitory concentration)against A549 cells was 15.68 μmol/L at pH 6.6 and was greater than 100 μmol/L at pH 7.4.At pH 6.6,pHTP-2 could act on various lung cancer cell lines and induce the death of A549 cells by rapid ly-sis;at pH 7.4,500 μmol/L pHTP-2 had weak toxicity to red blood cells(the hemolysis rate was ap-proximately 38％)and primary myocardial cells(the inhibition rate was 49.7％,with P＜0.05).Analy-sis of its charge,particle size,morphology,and secondary structure showed that at pH 6.6,the histidine in the sequence of pHTP-2 was protonated,increasing the positive charge(P＜0.01),decreasing the hy-drated particle size(P＜0.05)and forming an α-helical structure to induce membrane lysis of A549 cells.At pH 7.4,it was deprotonated,the positive charge decreases,a β-sheet structure was formed and self-aggregation occurred,limiting its effect on the A549 cell membrane and showing weak activity.In summary,pHTP-2 could respond to the weakly acidic microenvironment of tumors to exert selective cyto-toxic activity,effectively overcoming the shortcomings of anticancer peptides such as low efficiency and high toxicity.Our findings suggest that it is a high-quality lead molecule for anticancer drugs.

Aim To investigate the effect of linarin on improving cognitive behavior of APP/PS1 mice,and to explore the therapeutic effect of linarin on A β deposi-tion and neuroinflammation and its correlation.Meth-ods APP/PS1 transgenic mice were randomly divid-ed into the model group,high-dose group,medium-dose group,low-dose group and positive control group.C57BL/6J mice were set as the normal group.Morris water maze was used to evaluate the learning and mem-ory abilities of mice.TUNEL staining was used to de-tect the apoptosis of neurons in the CA1 region of mice.IHC was used to detect the expression levels of Aβ42 and GFAP.Western blot was used to detect the expression levels of BACE1 and PS-1.Results Com-pared with the normal group,mice of the model group showed lower NCP,shorter target quadrant travel,less target quadrant residence time percentage(all P＜0.01),higher apoptosis rate of neurons in the CA1 re-gion(P＜0.01),significantly higher protein expres-sion levels of A β42 and GFAP(all P＜0.01),and significantly higher protein expression levels of BACE1 and PS-1(all P＜0.01).Compared with the model group,the medium-dose group,high-dose group and positive control group showed higher NCP,longer tar-get quadrant travel,more target quadrant residence time percentage(all P＜0.05),lower apoptosis rate of neurons in the CA1 region(P＜0.01),significantly lower protein expression levels of A β42 and GFAP(all P＜0.01),and significantly lower protein expression levels of BACE1 and PS-1(all P＜0.01).Conclu-sions Linarin can inhibit two key enzymes to reduce the decomposition of APP and the generation of A β42,thereby inhibiting the activation of astrocytes,allevia-ting neuroinflammation,improving the core pathologi-cal features of AD,and thus significantly improving learning and memory impairment in APP/PS1 mice.

AIM To investigate the effects of Rutong Ruanjian Tablets on angiogenesis in cancer tissues of rats with preneoplastic breast cancer(PBC).METHODS 60 female SD rats were randomly divided into a blank group of 10 rats and a model group of 50 rats for the establishment of the PBC models of Liver-Qi Stagnation and Blood Stasis Pattern with 9 weeks of oral administration of 7,12-dimethylbenz[a]anthracene(DMBA)and cervical ligation.After successful modeling,the rats were randomly divided into the model group,the tamoxifen group(3.2 mg/kg),the Rutong Ruanjian Tablets group(128 mg/kg),the 3,5-difluorobenzoyl group(DAPT,5 mg/kg),and the Rutong Ruanjian Tablets(128 mg/kg via gavage)+DAPT(5 mg/kg intraperitoneal injection)group,for 1 month corresponding drug administration,with 10 rats in each group.Then the rats had their cancer progression and syndrome scores observed;their angiogenesis evaluated by assessment of microvascular density(MVD);their vascular endothelial growth factor(VEGF)expression assessed by immunohistochemistry;and their mRNA and protein expressions of proteins related to the DLL4/Notch1/Hes1 pathway measured using RT-qPCR,immunohistochemistry and Western blot.RESULTS During carcinogenesis of rats induced by DMBA,there was gradual disappearance of E-cadherin expression and consistency of HE staining result with the PBC progression confirming the success of the modeling.Compared with the blank group,the model group showed increased MVD values,mRNA expression of Notch1 and Hes1,and protein expressions of VEGF,DLL4,Notch1 and Hes1(P＜0.05,P＜0.01).Compared with the model group,the Rutong Ruanjian Tablets group exhibited reduced MVD values,mRNA expression of Notch1 and Hes1,and protein expressions of VEGF,DLL4,Notch1 and Hes1(P＜0.05,P＜0.01).The Rutong Ruanjian Tablets+DAPT group showed reduced mRNA expression of Notch1 and Hes1,and protein expressions of DLL4,Notch1 and Hes1 compared to the Rutong Ruanjian Tablets group(P＜0.05,P＜0.01).CONCLUSION Rutong Ruanjian Tablets can inhibit angiogenesis and attenuate cancer progression in PBC rats of Liver-Qi Stagnation and Blood Stasis Pattern,and the mechanism may lie in the downregulation of DLL4/Notch1/Hes1 signaling pathway related proteins.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

The interactions between microorganisms and medicinal plants are crucial to the quality improvement of medicinal plants. Medicinal plants attract microorganisms to colonize by secreting specific compounds and provide niche and nutrient support for these microorganisms, with a symbiotic network formed. These microorganisms grow in the rhizosphere, phyllosphere, and endophytic tissues of plants and significantly improve the growth performance and medicinal component accumulation of medicinal plants by promoting nutrient uptake, enhancing disease resistance, and regulating the synthesis of secondary metabolites. Microorganisms are also widely used in the ecological planting of medicinal plants, and the growth conditions of medicinal plants are optimized by simulating the microbial effects in the natural environment. The interactions between microorganisms and medicinal plants not only significantly improve the yield and quality of medicinal plants but also enhance their geoherbalism, which is in line with the concept of green agriculture and eco-friendly development. This study reviewed the research results on the interactions between medicinal plants and microorganisms in recent years and focused on the analysis of the great potential of microorganisms in optimizing the growth environment of medicinal plants, regulating the accumulation of secondary metabolites, inducing systemic resistance, and promoting the ecological planting of medicinal plants. It provides a scientific basis for the research on the interactions between medicinal plants and microorganisms, the research and development of microbial agents, and the application of microorganisms in the ecological planting of medicinal plants and is of great significance for the quality improvement of medicinal plants and the green and sustainable development of TCM resources.
Plants, Medicinal/metabolism* ; Bacteria/genetics* ; Symbiosis

This study investigated the therapeutic effects of Yiguanjian on dry eye in rats and its mechanisms involving the T helper cell 17(Th17)/regulatory T cell(Treg) balance. The rat model of dry eye was established by administrating 0.2% benzalkonium chloride solution in eye drops. After successful modeling, the rats were treated with Yiguanjian for 4 consecutive weeks. The Schirmer test was carried out to assess the lacrimal gland function, corneal fluorescence staining to detect corneal injury, hematoxylin-eosin staining to observe corneal histopathology, enzyme-linked immunosorbent assay to measure serum levels of interleukin(IL)-6, IL-8, IL-17A, IL-21, and tumor necrosis factor-α(TNF-α), RT-qPCR to analyze mRNA levels of retinoic acid receptor-related orphan receptor gamma t(RORγt) and forkhead box protein p3(Foxp3) in the corneal tissue, immunofluorescence double staining to evaluate RORγt and Foxp3 expression in the lacrimal gland tissue, and Western blot to quantify the protein levels of signal transducer and activator of transcription 3(STAT3), phosphorylated STAT3(p-STAT3), Janus kinase 2(Jak2), phosphorylated Jak2(p-Jak2), RORγt, and Foxp3 in the corneal tissue. The results demonstrated that Yiguanjian increased tear secretion(P<0.01), alleviated corneal damage and pathological changes, and lowered the serum levels of IL-6, IL-8, IL-17A, IL-21, and TNF-α(P<0.05) in model rats. Additionally, Yiguanjian decreased the ratio of RORγt to Foxp3 in the corneal and lacrimal gland tissue(P<0.01), downregulated the protein levels of STAT3, Jak2, and RORγt(P<0.05), upregulated the protein level of Foxp3(P<0.05), and inhibited phosphorylation of STAT3 and Jak2(P<0.01). These findings indicate that Yiguanjian ameliorates ocular surface dysfunction in dry eye rats by restoring Th17/Treg balance in the corneal and lacrimal gland tissue and suppressing systemic inflammatory cytokine release, thus mitigating ocular surface inflammation.
Animals ; Rats ; T-Lymphocytes, Regulatory/immunology* ; Drugs, Chinese Herbal/administration & dosage* ; Th17 Cells/immunology* ; Male ; Rats, Sprague-Dawley ; Dry Eye Syndromes/genetics* ; Nuclear Receptor Subfamily 1, Group F, Member 3/immunology* ; Lacrimal Apparatus/immunology* ; Humans ; STAT3 Transcription Factor/immunology*