Clinical Implications of Interleukin-4 and C-reactive Protein in Atopic Dermatitis and Their Changes Before and after Dupilumab Treatment.

Objective: To analyze the clinical implications of C-reactive protein (C-reactive protein) and interleukin-4 (IL-4) in atopic dermatitis and their correlations with the therapeutic effect of Dupilumab (DU). Methods: Seventy-four cases of atopic dermatitis (intervention group) were admitted to Xingtai Third Hospital between May 2021 and January 2023, and 55 concurrent healthy controls (control group) were selected as research participants. Atopic dermatitis patients were treated with a DU injection of 600 mg for the first time after diagnosis. Peripheral blood IL-4 and C-reactive protein levels before and after treatment in the intervention group and their levels at admission in the control group were comparatively analyzed, and their predictive value for the occurrence, clinical efficacy, and adverse reactions of atopic dermatitis were determined. Additionally, alterations in C-reactive protein and IL-4 levels before and after treatment in the intervention group and their relationship with the Scoring Atopic Dermatitis (SCORAD) index were discussed. Results: The intervention group exhibited higher C-reactive protein and IL-4 levels than the control group. The diagnostic sensitivity and specificity of C-reactive protein + IL-4 detection for atopic dermatitis were 74.32% and 94.55%, respectively (P < .05). The post-treatment C-reactive protein and IL-4 were lower in the intervention group, and the test results were positively correlated with SCORAD before and after treatment (P < .05). In addition, C-reactive protein + IL-4 detection showed excellent predictive effects on the therapeutic efficacy of DU and adverse reactions. Conclusions: IL-4 and C-reactive protein are closely related to atopic dermatitis, which can be used as the evaluation indexes for disease development of atopic dermatitis and therapeutic effects of DU in the future.

Molecular mechanism of PANoptosis in diagnostic markers and subtyping of osteoporosis / 中国组织工程研究

BACKGROUND:It has been hypothesized that PANoptosis may be involved in the pathologic process of osteoporosis,but there have been no studies addressing the mechanisms of PANoptosis genes in osteoporosis. OBJECTIVE:To analyze the biological mechanism of PANoptosis regulators in the occurrence and development of osteoporosis. METHODS:The GSE56815 dataset was obtained from the Gene Expression Omnibus database and PANoptosis genes were extracted for differential analysis.The key genes of PANoptosis were screened by random forest tree model to construct a disease risk prediction model.Consensus clustering algorithm,single sample genome enrichment analysis and immune infiltration analysis were used to explore the differences between different PANoptosis molecular subtypes.Herbal drugs that regulate the key genes of PANoptosis were predicted through Coremine medical database,a medical ontology information retrieval platform. RESULTS AND CONCLUSION:Based on the four PANoptosis key genes(CASP1,CASP10,MEFV,and TNF),the diagnostic markers of osteoporosis were determined,and the risk prediction model was constructed and verified.Osteoporosis was divided into two different PANoptosis subtypes(clusters A,B and gene clusters A,B),and the PANoptosis scores of cluster B and gene cluster B were higher than those of cluster A and gene cluster A,respectively.Traditional Chinese drugs such as ginseng which can regulate the key genes of PANoptosis were predicted by the Coremine medical database.

Biomimetic Nano-Immunoactivator via Ionic Metabolic Modulation for Strengthened NIR-II Photothermal Immunotherapy.

Reprogramming the immunologically "cold" environment of solid tumors is currently becoming the mainstream strategy to elicit powerful and systemic anticancer immunity. Here, a facile and biomimetic nano-immunnoactivator (CuS/Z@M4T1 ) is detailed by engineering a Zn2+ -bonded zeolitic imidazolate framework-8 (ZIF-8) with CuS nanodots (NDs) and cancer cell membrane for amplified near-infrared-II (NIR-II) photothermal immunotherapy via Zn2+ metabolic modulation. Taking advantage of the NIR-II photothermal effect of CuS NDs and the acidic responsiveness of ZIF-8, CuS/Z@M4T1 rapidly causes intracellular Zn2+ pool overload and disturbs the metabolic flux of 4T1 cells, which effectively hamper the production of heat shock proteins and relieve the resistance of photothermal therapy (PTT). Thus, amplified immunogenic cell death is evoked and initiates the immune cascade both in vivo and in vitro as demonstrated by dendritic cells maturation and T-cell infiltration. Further combination with antiprogrammed death 1 (aPD-1) achieves escalated antitumor efficacy which eliminates the primary, distant tumor and avidly inhibits lung metastasis due to cooperation of enhanced photothermal stimulation and empowerment of cytotoxic T lymphocytes by aPD-1. Collectively, this work provides the first report of using the intrinsic modulation property of meta-organometallic ZIF-8 for enhanced cancer photoimmunotherapy together with aPD-1, thereby inspiring a novel combined paradigm of ion-rich nanomaterials for cancer treatment.

Proteomic advance of ischemic stroke: preclinical, clinical, and intervention.

Ischemic stroke (IS) is the most common type of stroke and is characterized by high rates of mortality and long-term injury. The prediction and early diagnosis of IS are therefore crucial for optimal clinical intervention. Proteomics has provided important techniques for exploring protein markers associated with IS, but there has been no systematic evaluation and review of research that has used these techniques. Here, we review the differential proteins that have been found in cell- and animal- based studies and clinical trials of IS in the past 10 years; determine the key pathological proteins that have been identified in clinical trials; summarize the target proteins affected by interventions aimed at treating IS, with a focus on traditional Chinese medicine treatments. Overall, we clarify findings and problems that have been identified in recent proteomics research on IS and provide suggestions for improvements in this area. We also suggest areas that could be explored for determining the pathogenesis and developing interventions for IS.

Qi-Dong-Huo-Xue-Yin balances the immune microenvironment to protect against LPS induced acute lung injury.

COVID-19 induces acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) and leads to severe immunological changes that threatens the lives of COVID-19 victims. Studies have shown that both the regulatory T cells and macrophages were deranged in COVID-19-induced ALI. Herbal drugs have long been utilized to adjust the immune microenvironment in ALI. However, the underlying mechanisms of herbal drug mediated ALI protection are largely unknown. This study aims to understand the cellular mechanism of a traditional Chinese medicine, Qi-Dong-Huo-Xue-Yin (QD), in protecting against LPS induced acute lung injury in mouse models. Our data showed that QD intrinsically promotes Foxp3 transcription via promoting acetylation of the Foxp3 promoter in CD4+ T cells and consequently facilitates CD4+CD25+Foxp3+ Tregs development. Extrinsically, QD stabilized ß-catenin in macrophages to expedite CD4+CD25+Foxp3+ Tregs development and modulated peripheral blood cytokines. Taken together, our results illustrate that QD promotes CD4+CD25+Foxp3+ Tregs development via intrinsic and extrinsic pathways and balanced cytokines within the lungs to protect against LPS induced ALI. This study suggests a potential application of QD in ALI related diseases.

Three unprecedented thioether-linked dimeric pyrimidines isolated from the medicinal-edible herb Ligusticum striatum DC.

Three unprecedented thioether-linked dimeric pyrimidines, namely ligusticumines A-C, together with twelve known compounds were isolated and identified from the traditional Chinese medicinal-edible herb, Ligusticum striatum DC. The structures of all the isolated compounds were determined from NMR, HRESIMS and X-ray diffraction spectroscopies. Additionally, a novel 3-step synthetic route was developed to synthesize ligusticumine C by substitution, thiolation and coupling, with an overall yield of 5.4%. The inhibitory activities of the isolated compounds against phosphatidylinositol 3-kinase (PI3K) were tested, of which, (3S)-butylphthalide, a characteristic component of L. striatum, showed a potent inhibitory effect on PI3Kα (IC50: 3.6 µg/mL).

Mn3O4@polyaniline nanocomposite with multiple active sites to capture uranium(VI) and iodide: synthesis, performance, and mechanism.

A major challenge for radioactive wastewater treatment and associated environmental remediation is how to simultaneously remove cationic and anionic radionuclides. Herein, a series of Mn3O4@polyaniline (Mn3O4@PANI) nanocomposites were successfully prepared and used to remove U(VI) and I- from aqueous solution, two highly concomitant species in nuclear pollution settings. Batch adsorption experiments reveal that the component Mn3O4 is predominantly responsible for U(VI) removal, but PANI for I-. The nanocomposite with 24.2 wt% Mn3O4 possesses high removal percentages (> 85%) either for U(VI) or I- over a wide pH range, fast removal kinetics, and excellent adsorption selectivity at high concentrations of competing ions. Benefiting from the contributions of the two components and the high adsorption affinities, the nanocomposite achieves the simultaneous removal to coexisting U(VI) and I-, with a maximum adsorption capacity 102.6 mg/g for U(VI) and 126.1 mg/g for I-. X-ray photoelectron spectroscopy (XPS) results reveal that the U(VI) adsorption occurs via coordination bonding with Mn-O, -NH- , and =N- groups in the nanocomposite, whereas I- adsorption proceeds mainly through I anionic species exchange with Cl- and interactions with π-bonds in PANI, as well as the electrostatic attraction onto Mn3O4. Considering the excellent performance and multiple active sites, the Mn3O4@PANI nanocomposite is promising to remove practical radioactive U(VI) and I-.

SDF-1/CXCR4-Mediated Stem Cell Mobilization Involved in Cardioprotective Effects of Electroacupuncture on Mouse with Myocardial Infarction.

Stem cell-based therapeutic strategies have obtained a significant breakthrough in the treatment of cardiovascular diseases, particularly in myocardial infarction (MI). Nevertheless, limited retention and poor migration of stem cells are still problems for stem cell therapeutic development. Hence, there is an urgent need to develop new strategies that can mobilize stem cells to infarcted myocardial tissues effectively. Electroacupuncture (EA) intervention can improve cardiac function and alleviate myocardial injury after MI, but its molecular mechanism is still unclear. This study is aimed at observing the effects of EA treatment on the stem cell mobilization and revealing possible mechanisms in the MI model of mice. EA treatment at Neiguan (PC6) and Xinshu (BL15) acupoints was conducted on the second day after the ligation surgery. Then, the number of stem cells in peripheral blood after EA in MI mice and their cardiac function, infarct size, and collagen deposition was observed. We found that the number of CD34-, CD117-, Sca-1-, and CD90-positive cells increased at 6 h and declined at 24 h after EA intervention in the blood of MI mice. The expression of CXC chemokine receptor-4 (CXCR4) protein was upregulated at 6 h after EA treatment, while the ratio of LC3B II/I or p-ERK/ERK showed a reverse trend. In addition, there was obvious difference in EF and FS between wild-type mice and CXCR4+/- mice. The infarct size, collagen deposition, and apoptosis of the injured myocardium in CXCR4+/- mice increased but could be ameliorated by EA. In a word, our study demonstrates that EA alleviates myocardial injury via stem cell mobilization which may be regulated by the SDF-1/CXCR4 axis.

Tubiechong：A review on ethnomedicinal uses, bioactive chemical constituents and pharmacological activities.

ETHNOPHARMACOLOGICAL RELEVANCE: Tubiechong comprises mainly Eupolyphaga and Steleophaga is widely distributed in China. It has been used in the traditional medicine systems in Asian countries specially in China，Japan and Singapore for thousand years. AIM OF THE REVIEW: The aim of this work is to review the scientific work about Tubiechong regarding their ethnomedicinal uses, bioactive chemical constituents and pharmacological activities. MATERIALS AND METHODS: Relevant literature of Tubiechong was collected for its traditional uses, pharmacological activities, and bioactive compounds released from inception until May 2022. The online databases such as Web of Science, PubMed, Google Scholar, Science Direct, Scopus, SciFinder Scholar, Springer Link, China National Knowledge Infrastructure (CNKI), Wanfang Data, and VIP database were used as electronic search engines for articles with the various specific keywords. Additionally, references from ancient texts and local information such as PhD and MSc theses, books, and Chinese journals were also included. RESULTS: The clinical researches have revealed that Tubiechong alone has been successfully used to treat bone disease, ache, sprain, herpes zoster, paronychia and so on. Tubichong's main clinical application is to form formulations with other herbs. The most widely used 34 kinds of Chinese patent medicine containing Tubiechong were included in Chinese Pharmacopoeia (2020 Edition) for the treatment of traumatic injury, low back pain, cardiovascular disease, tumors or mass and nodule, cervical spondylopathy, osteoarthritis and psoriasis. Its other derived formulas have been used in the clinical treatment of various diseases, such as blood stasis, hepatic cirrhosis, cyclomastopathy, chronic active hepatitis, nephropathy, gynaecopathia, cancer diseases. To date, the bioactive substances reported are limited to protein and peptides, fatty acids, polysaccharides and alkaloids from Eupolyphaga sinensis Walker. So far, the pharmacological activities of Tubiechong and its various extracts have been evaluated, including anticoagulant and antithrombotic, anticancer, bone repair, immunomodulation, analgesia, antioxidant, antihyperlipidemic, antimicrobial and protective and repair functions for damage to the liver, heart, brain and skin. As an edible insect, its safety has also been confirmed by acute toxicity tests and 30-day feeding trials. CONCLUSION: Tubiechong is an important insect medicine with the effect of promoting blood circulation and removing blood stasis, which has been used in traditional Chinese medicine for thousands of years for the treatment of trauma and abdominal lumps, and has now been clinically extended to the treatment of a variety of diseases. Its multiple pharmacological activities indicate that it has great potential for development and application. However, its chemical constituents with pharmacological activity require further excavation and detailed study. In addition, the in-depth molecular pharmacological mechanisms deserve further explanation.

Anti-inflammatory and PTP1B inhibitory sesquiterpenoids from the twigs and leaves of Aglaia lawii.

Twelve sesquiterpenoids with seven different carbon skeletons, including four isodaucanes (1-4), an aromadendrane (5), a guaiane (6), a cadalane (7), two eudesmanes (8 and 9), two bisabolanes (10 and 11), and a megastigmane (12), were isolated from the twigs and leaves of Aglaia lawii (Wight) C. J. Saldanha et Ramamorthy. Of these compounds, amouanglienoids A (1) and B (2) are new isodaucane sesquiterpenoids. This is the first report of isodaucanes from the genus Aglaia, and amouanglienoid A (1) represents the first isodaucane containing a Δ7(8) double bond. Their structures were discerned from extensive spectroscopic analyses, single-crystal X-ray diffraction, and comparison of the experimental and calculated ECD data. In in vitro bioassays, compounds 1, 10, and 11 showed potent inhibitory effects against lipopolysaccharide (LPS)-induced inflammation in BV-2 microglial cells, while compound 11 exhibited considerable inhibition of PTP1B with an IC50 value of 16.05 ± 1.09 µM.

Phenolic Constituents, Antioxidant and Cytoprotective Activities, Enzyme Inhibition Abilities of Five Fractions from Vaccinium dunalianum Wight.

The bud of Vaccinium dunalianum Wight has been traditionally consumed as health herbal tea by "Yi" people in Yunnan Province, China, which was locally named "Que Zui tea". This paper studied the chemical constituents of five fractions from Vaccinium dunalianum, and their enzyme inhibitory effects of α-glucosidase and pancreatic lipase, antioxidant activity, and cytoprotective effects on H2O2-induced oxidative damage in HepG2 cells. The methanol extract of V. dunalianum was successively partitioned with petroleum ether (PF), chloroform (CF), ethyl acetate (EF), n-butanol (BF), and aqueous (WF) to obtain five fractions. The chemical profiling of the five fractions was analyzed by ultra-high-performance liquid chromatography coupled with a tandem mass spectrometry (UHPLC-MS/MS), and 18 compounds were tentatively identified. Compared to PF, CF, BF and WF, the EF revealed the highest total phenols (TPC) and total flavonoids (TFC), and displayed the strongest enzyme inhibition ability (α-glucosidase and pancreatic lipase) and antioxidant capacity (DPPH, ABTS and FRAP). Furthermore, these five fractions, especially EF, could effectively inhibit reactive oxygen species (ROS) production and cell apoptosis on H2O2-induced oxidative damage protection in HepG2 cells. This inhibitory effect might be caused by the up-regulation of intracellular antioxidant enzyme activity (CAT, SOD, and GSH). The flavonoids and phenolic acids of V. dunalianum might be the bioactive substances responsible for enzyme inhibitory, antioxidant, and cytoprotective activities.

6'-O-Caffeoylarbutin from Que Zui tea ameliorates acetaminophen-induced liver injury via enhancing antioxidant ability and regulating the PI3K signaling pathway.

Que Zui tea (QT), a traditional herbal tea in China, has a significant hepatoprotective effect. 6'-O-Caffeoylarbutin (CA) is the most abundant chemical compound in the QT. However, the hepatoprotective effect of CA has not been investigated. This study is aimed to evaluate the protective effect of CA on acetaminophen (APAP) induced hepatotoxicity in vivo and in vitro and its possible underlying mechanism. In APAP-induced HepG-2 cells, CA inhibited intracellular ROS accumulation and cell apoptosis, and improved the expression of antioxidants including SOD, CAT and GSH. In APAP-administrated mice, CA pretreatment remarkably ameliorated the histopathological damage and inflammatory response, and antioxidant enzyme activity in the serum and liver tissues. Moreover, the immunohistochemistry and immunofluorescence assay results revealed that the CA markedly reduced ROS production and apoptosis, and activated antioxidant transcription factor Nrf2 in the liver. Meanwhile, molecular docking results showed that the strong binding force of CA and PI3K was due to the higher number of hydrogen- and π-bonds with active site residues. Notably, CA pretreatment significantly regulated the expression of PI3K, Akt, Nrf2, NQO1, HO-1, Bcl-2, Bax, caspase-3, and caspase-9 proteins in APAP-treated liver tissues. These data demonstrated that CA had a protective effect against APAP-induced hepatotoxicity via regulating the PI3K/Akt and Nrf2 signaling pathway.

Effect of Antioxidants Supplementation on Erectile Dysfunction: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: In Erectile dysfunction (ED) patients, phosphodiesterase type 5 (PDE5) inhibitors are considered as the first-line therapy. However, 30-50% of ED patients fail to follow this therapeutic option because of adverse events, lack of efficacy, or drug costs. Antioxidant supplementation is widely applied in clinical practice and viewed as a potential therapeutic option for ED. Therefore, it is attractive to assess the effect of antioxidants supplementation on ED patients. OBJECTIVES: To evaluate the effects of antioxidants supplementation on ED. METHODS: Published randomized controlled trials of antioxidants in ED were searched in the PubMed, Embase, and Cochrane Library databases from inception to October 3, 2021. Meta-analyses were carried out using a random-effects model. The results were presented as standard mean differences (SMDs) with their 95% confidence intervals (CIs). RESULTS: Eighteen studies with 1,331 ED patients were included in the study. Compared with placebo, antioxidants alone treatment showed a statistical increase in International Index of Erectile Function (IIEF) score (SMD = 1.93; 95% CI: 0.15, 3.72; P = .034). Compared with placebo, antioxidants compound treatment elicited a significant increase in IIEF score (SMD = 2.74; 95% CI: 1.67, 3.81; P < .001) as well as sexual satisfaction score (SMD = 1.61; 95% CI: 0.63, 2.59; P = .001). Compared with the PDE5 inhibitors alone, combination of PDE5 inhibitors and antioxidants showed a significant increase in IIEF score (SMD = 1.1; 95% CI: 0.51, 1.68; P < .001) and sexual satisfaction score (SMD = 1.28; 95% CI: 0.06, 2.51; P = .04). CONCLUSION: This study found that the effect of antioxidant alone treatment on ED may be limited. However, antioxidant compound treatment, as well as combination of PDE5 inhibitors and antioxidants, were associated with improved ED, and can be considered as an accessary therapeutic option for ED. Su L, Yang Z, Qu H, et al. Effect of Antioxidants Supplementation on Erectile Dysfunction: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Sex Med Rev 2022;10:754-763.

Exosome-Mediated miR-21 Was Involved in the Promotion of Structural and Functional Recovery Effect Produced by Electroacupuncture in Sciatic Nerve Injury.

PURPOSE: Our study is aimed at investigating the mechanism by which electroacupuncture (EA) promoted nerve regeneration by regulating the release of exosomes and exosome-mediated miRNA-21 (miR-21) transmission. Furthermore, the effects of Schwann cells- (SC-) derived exosomes on the overexpression of miR-21 for the treatment of PNI were investigated. METHODS: A sciatic nerve injury model of rat was constructed, and the expression of miR-21 in serum exosomes and damaged local nerves was detected using RT-qPCR after EA treatment. The exosomes were identified under a transmission electron microscope and using western blotting analysis. Then, the exosome release inhibitor, GW4869, and the miR-21-5p-sponge used for the knockdown of miR-21 were used to clarify the effects of exosomal miR-21 on nerve regeneration promoted by EA. The nerve conduction velocity recovery rate, sciatic nerve function index, and wet weight ratio of gastrocnemius muscle were determined to evaluate sciatic nerve function recovery. SC proliferation and the level of neurotrophic factors were assessed using immunofluorescence staining, and the expression levels of SPRY2 and miR-21 were detected using RT-qPCR analysis. Subsequently, the transmission of exosomal miR-21 from SC to the axon was verified in vitro. Finally, the exosomes derived from the SC infected with the miR-21 overexpression lentivirus were collected and used to treat the rat SNI model to explore the therapeutic role of SC-derived exosomes overexpressing miR-21. RESULTS: We found that EA inhibited the release of serum exosomal miR-21 in a PNI model of rats during the early stage of PNI, while it promoted its release during later stages. EA enhanced the accumulation of miR-21 in the injured nerve and effectively promoted the recovery of nerve function after PNI. The treatment effect of EA was attenuated when the release of circulating exosomes was inhibited or when miR-21 was downregulated in local injury tissue via the miR-21-5p-sponge. Normal exosomes secreted by SC exhibited the ability to promote the recovery of nerve function, while the overexpression of miR-21 enhanced the effects of the exosomes. In addition, exosomal miR-21 secreted by SC could promote neurite outgrowth in vitro. CONCLUSION: Our results demonstrated the mechanism of EA on PNI from the perspective of exosome-mediated miR-21 transport and provided a theoretical basis for the use of exosomal miR-21 as a novel strategy for the treatment of PNI.

Response of carbon, nitrogen and phosphorus concentration and stoichiometry of plants and soils during a soybean growth season to O3 stress and straw return in Northeast China.

Carbon (C), nitrogen (N) and phosphorus (P) concentrations and stoichiometry play important roles in biogeochemical cycles of the ecosystems, yet it is still unclear how the allocations of C, N and P concentrations and stoichiometry among plant organs and soils related to O3 stress and straw return. Here, a pot experiment was conducted in open top chambers to monitor the response of C, N and P concentrations and stoichiometry of leaves, stems, roots and soils during a growing season (branching, flowering and podding stages) of soybean (Glycine max; a species highly sensitive to O3) to background O3 concentration (44.8 ± 5.6 ppb), O3 stress (79.7 ± 5.4 ppb) and straw treatment (no straw return and straw return). O3 stress significantly decreased root biomass. Straw return significantly increased root biomass under O3 stress at branching and flowering stages. Generally, O3 stress and straw return showed significant effects on the C, N and P concentrations of leaves and soils, and stoichiometric ratios of leaves, stems and microbial biomass. The C, N and P concentrations and stoichiometry of leaves, stems, roots and soils in response to O3 stress and straw return at the branching stage were inconsistent with the changes observed at the flowering and podding stages. The P conversion efficiency showed significant relationship with root P concentration under the combined effects of O3 stress and straw return. Altogether, the present study indicated that C, N and P concentrations of soybean might be more important than stoichiometric ratios as a driver of root defence against O3 stress in the case of straw return.

Acteoside, the Main Bioactive Compound in Osmanthus fragrans Flowers, Palliates Experimental Colitis in Mice by Regulating the Gut Microbiota.

The present study investigated the effects of Osmanthus fragrans flowers and acteoside on murine colitis and the underlying mechanisms. The O. fragrans flower extract (OFE) and acteoside were administrated to chemically induced colitic mice. The results showed that OFE or acteoside ameliorates intestinal inflammation, oxidative stress, and activation of nuclear factor-κB (NF-κB) in colitic mice. The dysbiosis of the gut microbiome in colitic mice was also partly restored by OFE or acteoside, which was characterized by the alteration of the gut microbiome structure and the enrichment of beneficial bacteria (Akkermansia muciniphila and Bacteroides thetaiotaomicron). Dextran sulfate sodium (DSS)-induced gut metabolome dysfunctions (e.g., sphingosine metabolism and amino acids metabolism) in colitic mice were also partly restored by OFE and acteoside. A fecal microbiota (FM) transplantation study suggested that, compared with the FM from the normal diet-dosed donor mice, the FM from the OFE- or acteoside-dosed donor mice significantly suppressed colitic symptoms.

Hypoglycemic and hypolipidemic effects of Epigynum auritum in high fat diet and streptozotocin-induced diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Epigynum auritum is mainly distributed in Southwest China, and has been used as a "dai" folk medicine with promising Besides, the leaves and barks of E. auritum have detoxifying, analgesic and relieving swelling effects. Previous studies evidenced that E. auritum was rich in pregnanes and their glycosides. However, the hypoglycemic and hypolipidemic effects of the extract from E. auritum (EAE) and its molecular mechanism are still not studied. AIM OF THE STUDY: The aim of this study is to investigate the hypoglycemic and hypolipidemic effects of EAE on high-fat diet and streptozocin-induced type 2 diabetic rats. MATERIALS AND METHODS: The high-fat diet and streptozocin induced type 2 diabetic model was established. The diabetic rats were treated with 70% ethanol extract of E. auritum (100 and 300 mg/kg/d) or metformin (DMBG, 100 mg/kg/d) every day for 4 weeks. Fasting blood glucose was recorded weekly. The phenotypic changes were evaluated by the measurement of biochemical indexes and immunohistochemical. The expressions of signaling-related proteins were explored by western blotting. RESULTS: EAE could effectively regulate the metabolism of glucose and lipids in diabetic rats by increasing insulin sensitivity. In addition, EAE ameliorated the oxidative stress damage and further mitigated the liver, kidney, and pancreatic damage. Mechanism research results show that EAE treatment increased the phosphorylation of Akt, AMPK and GSK-3ß, up-regulated the expression of GLUT-2, GLUT-4 and PPAR-α, and reduced PPAR-γ and FAS expressions. CONCLUSION: EAE exhibited significant hypoglycemic and hypolipidemic effects in HFD/STZ-induced diabetes rats. The mechanism may be related to the effective upregulation of AMPK/Akt/GSK-3ß pathway and the decreased expression of PPAR-γ and FAS. It could be a promising natural product with potential value for the development of drugs to prevent or treat type 2 diabetic.

Anti-leukemic effect and molecular mechanism of 11-methoxytabersonine from Melodinus cochinchinensis via network pharmacology, ROS-mediated mitochondrial dysfunction and PI3K/Akt signaling pathway.

Melodinus cochinchinensis (Lour.) Merr. is a Yunnan endemic folk medicine. Our previous study showed that 11-methoxytabersonine (11-MT) isolated from M. cochinchinensis has strong cytotoxicity on human T-ALL cells, but its molecular mechanism has not been studied. In current study, the cytotoxicity and possible mechanism of 11-MT on T-cell acute lymphoblastic leukemia was explored using network pharmacology and molecular biology techniques. 11-MT significantly inhibited the cell proliferations on different four human T-ALL cells (MOLT-4, Jurkat, CCRF-CEM, and CEM/C1 cells). 11-MT triggered ROS accumulation, calcium concentration and cell apoptosis, and decreased the mitochondrial membrane potential (MMP) in human T-ALL cells, especially MOLT-4 cells. Western blot analysis showed that it can induce MOLT-4 cell apoptosis by up-regulating PI3K/Akt signaling pathway. Therefore, 11-MT induces human T-ALL cells apoptosis via up-regulation of ROS-mediated mitochondrial dysfunction and down-regulation of PI3K/Akt/mTOR signaling pathway.

Phenolic constituents, antioxidant activity and neuroprotective effects of ethanol extracts of fruits, leaves and flower buds from Vaccinium dunalianum Wight.

Vaccinium dunalianum Wight is an important healthy tea resource in China with health benefits. The chemical compositions and the possible bioactive substances in its fruits, leaves and flower buds extracts (FE, LE and FBE) were identified and characterized by UHPLC-HRMS/MS. Consequently, FE, LE and FBE were rich in phenolic and flavonoid compounds. Among them, 21 compounds were identified, and the main components were chlorogenic acid, quinic acid and 6'-O-caffeoylarbutin. Furthermore, their neuroprotection and mechanism on H2O2-induced neurotoxicity in PC12 cells were investigated. All the different concentrations of FE, LE and FBE were apparently inhibited the H2O2-induced ROS generation and apoptosis on PC12 cells. FBE showed stronger neuroprotective activity against H2O2-induced PC12 cell damage than those of FE and LE. The mechanism of neuroprotective effect might be related to the upregulation of endogenous antioxidant enzymes expressions and activation of the Nrf2/HO-1 signaling pathway.

Effect of Antioxidants Supplementation on Erectile Dysfunction: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: In Erectile dysfunction (ED) patients, phosphodiesterase type 5 (PDE5) inhibitors are considered as the first-line therapy. However, 30-50% of ED patients fail to follow this therapeutic option because of adverse events, lack of efficacy, or drug costs. Antioxidant supplementation is widely applied in clinical practice and viewed as a potential therapeutic option for ED. Therefore, it is attractive to assess the effect of antioxidants supplementation on ED patients. OBJECTIVES: To evaluate the effects of antioxidants supplementation on ED. METHODS: Published randomized controlled trials of antioxidants in ED were searched in the PubMed, Embase, and Cochrane Library databases from inception to October 3, 2021. Meta-analyses were carried out using a random-effects model. The results were presented as standard mean differences (SMDs) with their 95% confidence intervals (CIs). RESULTS: Eighteen studies with 1,331 ED patients were included in the study. Compared with placebo, antioxidants alone treatment showed a statistical increase in International Index of Erectile Function (IIEF) score (SMD = 1.93; 95% CI: 0.15, 3.72; P = .034). Compared with placebo, antioxidants compound treatment elicited a significant increase in IIEF score (SMD = 2.74; 95% CI: 1.67, 3.81; P < .001) as well as sexual satisfaction score (SMD = 1.61; 95% CI: 0.63, 2.59; P = .001). Compared with the PDE5 inhibitors alone, combination of PDE5 inhibitors and antioxidants showed a significant increase in IIEF score (SMD = 1.1; 95% CI: 0.51, 1.68; P < .001) and sexual satisfaction score (SMD = 1.28; 95% CI: 0.06, 2.51; P = .04). CONCLUSION: This study found that the effect of antioxidant alone treatment on ED may be limited. However, antioxidant compound treatment, as well as combination of PDE5 inhibitors and antioxidants, were associated with improved ED, and can be considered as an accessary therapeutic option for ED.