LanGui tea, an herbal medicine formula, protects against binge alcohol-induced acute liver injury by activating AMPK-NLRP3 signaling.

BACKGROUND: LanGui tea, a traditional Chinese medicine formulation comprising of Gynostemma pentaphyllum (Thunb.) Makino, Cinnamomum cassia (L.) J. Presl, and Ampelopsis grossedentata (Hand-Mazz) W.T. Wang, has yet to have its potential contributions to alcoholic liver disease (ALD) fully elucidated. Consequently, the objective of this research is to investigate the protective properties of LanGui tea against binge alcohol-induced ALD and the mechanisms underlying its effects. METHODS: An experimental model of acute alcohol-induced liver disease was performed to assess the protective effects of extract of LanGui tea (ELG) at both 50 and 100 mg.kg-1 dosages on male C57BL/6 mice. Various parameters, including hepatic histological changes, inflammation, lipids content, as well as liver enzymes and interleukin 1ß (IL-1ß) in the serum were measured. The pharmacological mechanisms of ELG, specifically its effects on adenosine monophosphate-(AMP)-activated protein kinase (AMPK) and NLR family pyrin domain containing 3 (NLRP3) signaling, were investigated through Western blotting, qRT-PCR, ELISA, immunohistochemistry, immunofluorescence analyses, and by blocking the AMPK activity. RESULTS: ELG demonstrated a mitigating effect on fatty liver, inflammation, and hepatic dysfunction within the mouse model. This effect was achieved by activating AMPK signaling and inhibitingNLRP3 signaling in the liver, causing a reduction in IL-1ß generation. In vitro studies further confirmed that ELG inhibited cell damage and IL-1ß production in ethanol-induced hepatocytes by enhancing AMPK-NLRP3 signaling. Conversely, the pharmacological inhibition of AMPK activity nearly abrogated such alteration. CONCLUSIONS: Thus, LanGui tea emerges as a promising herbal therapy for ALD management involving AMPK-NLRP3 signaling.

[Diosgenin alleviates NAFLD induced by a high-fat diet in rats via mTOR/SREBP-1c/HSP60/MCAD/SCAD signaling pathway].

This study aims to observe the effects of diosgenin on the expression of mammalian target of rapamycin(mTOR), sterol regulatory element-binding protein-1c(SREBP-1c), heat shock protein 60(HSP60), medium-chain acyl-CoA dehydrogenase(MCAD), and short-chain acyl-CoA dehydrogenase(SCAD) in the liver tissue of the rat model of non-alcoholic fatty liver disease(NAFLD) and explore the mechanism of diosgenin in alleviating NAFLD. Forty male SD rats were randomized into five groups: a control group, a model group, low-(150 mg·kg~(-1)·d~(-1)) and high-dose(300 mg·kg~(-1)·d~(-1)) diosgenin groups, and a simvastatin(4 mg·kg~(-1)·d~(-1)) group. The rats in the control group were fed with a normal diet, while those in the other four groups were fed with a high-fat diet. After feeding for 8 weeks, the body weight of rats in the high-fat diet groups increased significantly. After that, the rats were administrated with the corresponding dose of diosgenin or simvastatin by gavage every day for 8 weeks. The levels of triglyceride(TG), total cholesterol(TC), alanine transaminase(ALT), and aspartate transaminase(AST) in the serum were determined by the biochemical method. The levels of TG and TC in the liver were measured by the enzyme method. Oil-red O staining was employed to detect the lipid accumulation, and hematoxylin-eosin(HE) staining to detect the pathological changes in the liver tissue. The mRNA and protein levels of mTOR, SREBP-1c, HSP60, MCAD, and SCAD in the liver tissue of rats were determined by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR) and Western blot, respectively. Compared with the control group, the model group showed increased body weight, food uptake, liver index, TG, TC, ALT, and AST levels in the serum, TG and TC levels in the liver, lipid deposition in the liver, obvious hepatic steatosis, up-regulated mRNA and protein expression levels of mTOR and SREBP-1c, and down-regulated mRNA and protein expression levels of HSP60, MCAD, and SCAD. Compared with the model group, the rats in each treatment group showed obviously decreased body weight, food uptake, liver index, TG, TC, ALT, and AST levels in the serum, TG and TC levels in the liver, lessened lipid deposition in the liver, ameliorated hepatic steatosis, down-regulated mRNA and protein le-vels of mTOR and SREBP-1c, and up-regulated mRNA and protein levels of HSP60, MCAD, and SCAD. The high-dose diosgenin outperformed the low-dose diosgenin and simvastatin. Diosgenin may prevent and treat NAFLD by inhibiting the expression of mTOR and SREBP-1c and promoting the expression of HSP60, MCAD, and SCAD to reduce lipid synthesis, improving mitochondrial function, and promoting fatty acid ß oxidation in the liver.

[Research progress of the impacts of acupuncture on programmed cell death in treatment of ischemic stroke].

The new progress has been made in the research of programmed cell death (e.g. autophagy, apoptosis, pyroptosis, necroptosis and ferroptosis) for the pathological mechanism of ischemic stroke. As an important non-pharmacological therapy, acupuncture is widely used in stroke patients and has achieved favorable effect. The researches in recent years have shown that acupuncture plays its neuroprotective role on ischemic stroke by modulation of autophagy, apoptosis, pyroptosis, necroptosis and ferroptosis of neurons. Acupuncture is effective in treatment of ischemic stroke by regulating programmed cell death.

[Effect of diosgenin on mTOR/FASN/HIF-1α/VEGFA expression in rats with non-alcoholic fatty liver disease].

The present study aimed to investigate the effect of diosgenin on mammalian target of rapamycin(mTOR), fatty acid synthase(FASN), hypoxia inducible factor-1α(HIF-1α), and vascular endothelial growth factor A(VEGFA) expression in liver tissues of rats with non-alcoholic fatty liver disease(NAFLD) and explore the mechanism of diosgenin on lipogenesis and inflammation in NAFLD. Forty male SD rats were divided into a normal group(n=8) fed on the normal diet and an experimental group(n=32) fed on the high-fat diet(HFD) for the induction of the NAFLD model. After modeling, the rats in the experimental group were randomly divided into an HFD group, a low-dose diosgenin group(150 mg·kg~(-1)·d~(-1)), a high-dose diosgenin group(300 mg·kg~(-1)·d~(-1)), and a simvastatin group(4 mg·kg~(-1)·d~(-1)), with eight rats in each group. The drugs were continuously given by gavage for eight weeks. The levels of triglyceride(TG), total cholesterol(TC), low-density lipoprotein cholesterol(LDL-C), alanine transaminase(ALT), and aspartate transaminase(AST) in the serum were detected by the biochemical method. The content of TG and TC in the liver was detected by the enzyme method. Enzyme-linked immunosorbent assay(ELISA) was used to measure interleukin 1ß(IL-1ß) and tumor necrosis factor α(TNF-α) in the serum. Lipid accumulation in the liver was detected by oil red O staining. Pathological changes of liver tissues were detected by hematoxylin-eosin(HE) staining. The mRNA and protein expression levels of mTOR, FASN, HIF-1α, and VEGFA in the liver of rats were detected by real-time fluorescence-based quantitative polymerase chain reaction(PCR) and Western blot, respectively. Compared with the normal group, the HFD group showed elevated body weight and levels of TG, TC, LDL-C, ALT, AST, IL-1ß, and TNF-α(P<0.01), increased lipid accumulation in the liver(P<0.01), obvious liver steatosis, up-regulated mRNA expression levels of mTOR, FASN, HIF-1α, and VEGFA(P<0.01), and increased protein expression levels of p-mTOR, FASN, HIF-1α, and VEGFA(P<0.01). Compared with the HFD group, the groups with drug treatment showed lowered body weight and levels of TG, TC, LDL-C, ALT, AST, IL-1ß, and TNF-α(P<0.05, P<0.01), reduced lipid accumulation in the liver(P<0.01), improved liver steatosis, decreased mRNA expression levels of mTOR, FASN, HIF-1α, and VEGFA(P<0.05, P<0.01), and declining protein expression levels of p-mTOR, FASN, HIF-1α, and VEGFA(P<0.01). The therapeutic effect of the high-dose diosgenin group was superior to that of the low-dose diosgenin group and the simvastatin group. Diosgenin may reduce liver lipid synthesis and inflammation and potentiate by down-regulating the mTOR, FASN, HIF-1α, and VEGFA expression, playing an active role in preventing and treating NAFLD.

Acupuncture and Doxylamine-Pyridoxine for Nausea and Vomiting in Pregnancy : A Randomized, Controlled, 2 × 2 Factorial Trial.

BACKGROUND: An effective and safe treatment for nausea and vomiting of pregnancy (NVP) is lacking. OBJECTIVE: To assess the efficacy and safety of acupuncture, doxylamine-pyridoxine, and a combination of both in women with moderate to severe NVP. DESIGN: Multicenter, randomized, double-blind, placebo-controlled, 2 × 2 factorial trial. (ClinicalTrials.gov: NCT04401384). SETTING: 13 tertiary hospitals in mainland China from 21 June 2020 to 2 February 2022. PARTICIPANTS: 352 women in early pregnancy with moderate to severe NVP. INTERVENTION: Participants received daily active or sham acupuncture for 30 minutes and doxylamine-pyridoxine or placebo for 14 days. MEASUREMENTS: The primary outcome was the reduction in Pregnancy-Unique Quantification of Emesis (PUQE) score at the end of the intervention at day 15 relative to baseline. Secondary outcomes included quality of life, adverse events, and maternal and perinatal complications. RESULTS: No significant interaction was detected between the interventions (P = 0.69). Participants receiving acupuncture (mean difference [MD], -0.7 [95% CI, -1.3 to -0.1]), doxylamine-pyridoxine (MD, -1.0 [CI, -1.6 to -0.4]), and the combination of both (MD, -1.6 [CI, -2.2 to -0.9]) had a larger reduction in PUQE score over the treatment course than their respective control groups (sham acupuncture, placebo, and sham acupuncture plus placebo). Compared with placebo, a higher risk for births with children who were small for gestational age was observed with doxylamine-pyridoxine (odds ratio, 3.8 [CI, 1.0 to 14.1]). LIMITATION: The placebo effects of the interventions and natural regression of the disease were not evaluated. CONCLUSION: Both acupuncture and doxylamine-pyridoxine alone are efficacious for moderate and severe NVP. However, the clinical importance of this effect is uncertain because of its modest magnitude. The combination of acupuncture and doxylamine-pyridoxine may yield a potentially larger benefit than each treatment alone. PRIMARY FUNDING SOURCE: The National Key R&D Program of China and the Project of Heilongjiang Province "TouYan" Innovation Team.

[Complete chloroplast genome sequencing and phylogeny of wild Atractylodes lancea from Yuexi, Anhui province].

This study investigated the choroplast genome sequence of wild Atractylodes lancea from Yuexi in Anhui province by high-throughput sequencing, followed by characterization of the genome structure, which laid a foundation for the species identification, analysis of genetic diversity, and resource conservation of A. lancea. To be specific, the total genomic DNA was extracted from the leaves of A. lancea with the improved CTAB method. The chloroplast genome of A. lancea was sequenced by the high-throughput sequencing technology, followed by assembling by metaSPAdes and annotation by CPGAVAS2. Bioiformatics methods were employed for the analysis of simple sequence repeats(SSRs), inverted repeat(IR) border, codon bias, and phylogeny. The results showed that the whole chloroplast genome of A. lancea was 153 178 bp, with an 84 226 bp large single copy(LSC) and a 18 658 bp small single copy(SSC) separated by a pair of IRs(25 147 bp). The genome had the GC content of 37.7% and 124 genes: 87 protein-coding genes, 8 rRNA genes, and 29 tRNA genes. It had 26 287 codons and encoded 20 amino acids. Phylogenetic analysis showed that Atractylodes species clustered into one clade and that A. lancea had close genetic relationship with A. koreana. This study established a method for sequencing the chloroplast genome of A. lancea and enriched the genetic resources of Compositae. The findings are expected to lay a foundation for species identification, analysis of genetic diversity, and resource conservation of A. lancea.

Zinc deficiency associated with cutaneous toxicities induced by epidermal growth factor receptor tyrosine kinase inhibitor therapy in patients with lung adenocarcinoma.

PURPOSE: Cutaneous toxicities are common adverse effects following epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy. Zinc deficiency causes diverse diseases, including skin toxicities. Therefore, this study aimed to investigate the role of zinc deficiency in patients with EGFR-TKI-induced skin toxicities. EXPERIMENTAL DESIGN: This retrospective study enrolled 269 patients with diverse skin disorders who visited our hospital between January 2016 and December 2017. The skin toxicity severities and plasma zinc levels of 101 EGFR-TKI-treated cancer patients were analysed and compared with those of 43 non-EGFR-TKI-treated cancer patients and 125 patients without cancer but presenting cutaneous manifestations. Additionally, the role of zinc in erlotinib-induced skin eruptions was established in a 14-day-murine model. Clinical features were further evaluated following systemic zinc supplementation in EGFR-TKI-treated cancer patients. RESULTS: EGFR-TKI-treated patients demonstrated severe cutaneous manifestations and a significant decrease in plasma zinc levels than those of the control groups. The serum zinc level and Common Terminology Criteria for Adverse Events (CTCAE) 5.0 grading of EGFR-TKI-induced skin toxicities showed a significant negative correlation (r = -0.29; p < 0.0001). Moreover, erlotinib treatment decreased the plasma zinc levels and induced periorificial dermatitis in rats confirming zinc deficiency following EGFR-TKI treatment. Zinc supplementation to the EGFR-TKI-treated cancer patients showed a significant decrease in the CTCEA grading (p < 0.0005 for mucositis and p < 0.0.0001 for all other cases) after 8 weeks. CONCLUSIONS: Skin impairment following EGFR-TKI therapy could be ameliorated through zinc supplementation. Thus, zinc supplementation should be considered for cancer patients undergoing EGFR-TKI therapy.

Calcium-Dependent Protein Kinase 28 Maintains Potato Photosynthesis and Its Tolerance under Water Deficiency and Osmotic Stress.

Calcium-dependent protein kinases (CDPK) are implicated in signaling transduction in eukaryotic organisms. It is largely unknown whether StCDPK28 plays a role in the response to water deficiency and osmotic stress in potato plants (Solanum tuberosum L.). Potato cv. Zihuabai was cultivated under natural, moderate, and severe water deficiency conditions; to induce osmotic stress, potato plants were treated with 10% or 20% PEG. StCDPK28-overexpression and StCDPK28-knockdown plants were constructed. StCDPKs were evaluated by qRT-PCR. The subcellular location of the StCDPK28 protein was observed with confocal scanning laser microscopy. Phenotypic changes were indicated by photosynthetic activity, the contents of H2O2, MDA and proline, and the activities of CAT, SOD and POD. Results showed water deficiency and osmotic stress altered StCDPK expression patterns. StCDPK28 exhibited a membrane, cytosolic and nuclear localization. Water deficiency and osmotic stress induced StCDPK28 upregulation. Photosynthetic activity was enhanced by StCDPK28 overexpression, while decreased by StCDPK2 knockdown under water deficiency and osmotic stress. StCDPK28 overexpression decreased H2O2 and MDA, and increased proline, while StCDPK28 knockdown showed reverse results, compared with the wild type, in response to water deficiency and osmotic stress. StCDPK28 overexpression increased the activities of CAT, SOD and POD, while StCDPK28-knockdown plants indicated the reverse trend under water deficiency and osmotic stress conditions. Regulation of StCDPK28 expression could be a promising approach to improve the tolerance ability of potato plants in response to drought or high salt media.

The Angelica dahurica: A Review of Traditional Uses, Phytochemistry and Pharmacology.

Angelica dahurica (A. dahurica) root is a famous edible medicinal herb that has been used in China for thousands of years. To date, more than 300 chemical constituents have been discovered from A. dahurica. Among these ingredients, coumarins and volatile oils are the major active compounds. Moreover, a few other compounds have also been isolated from the root of A. dahurica, such as alkaloids, phenols, sterols, benzofurans, polyacetylenes and polysaccharides. Modern pharmacological studies demonstrated that the root of A. dahurica and its active components displayed various bioactivities such as anti-inflammation, anti-tumor, anti-oxidation, analgesic activity, antiviral and anti-microbial effects, effects on the cardiovascular system, neuroprotective function, hepatoprotective activity, effects on skin diseases and so on. Based on these studies, this review focused on the research publications of A. dahurica and aimed to summarize the advances in the traditional uses, phytochemistry and pharmacology which will provide reference for the further studies and applications of A. dahurica.

Genome-wide investigation and expression analysis of the AP2/ERF family for selection of agarwood-related genes in Aquilaria sinensis (Lour.) Gilg.

Aquilaria sinensis is an important non-timber tree species for producing high-value agarwood, which is widely used as a traditional medicine and incense. Agarwood is the product of Aquilaria trees in response to injury and fungal infection. The APETALA2/ethylene responsive factor (AP2/ERF) transcription factors (TFs) play important roles in plant stress responses and metabolite biosynthesis. In this study, 119 AsAP2/ERF genes were identified from the A. sinensis genome and divided into ERF, AP2, RAV, and Soloist subfamilies. Their conserved motif, gene structure, chromosomal localization, and subcellular localization were characterized. A stress/defense-related ERF-associated amphiphilic repression (EAR) motif and an EDLL motif were identified. Moreover, 11 genes that were highly expressed in the agarwood layer in response to whole-tree agarwood induction technique (Agar-Wit) treatment were chosen, and their expression levels in response to methyl jasmonate (MeJA), salicylic acid (SA), or salt treatment were further analyzed using the quantitative real time PCR (qRT-PCR). Among the 11 genes, eight belonged to subgroup B-3. All 11 genes were significantly upregulated under salt treatment, while eight genes were significantly induced by both MeJA and SA. In addition, the gene clusters containing these upregulated genes on chromosomes were observed. The results obtained from this research not only provide useful information for understanding the functions of AP2/ERF genes in A. sinensis but also identify candidate genes and gene clusters to dissect their regulatory roles in agarwood formation for future research.

Potential Natural Small Molecular Compounds for the Treatment of Chronic Obstructive Pulmonary Disease: An Overview.

Chronic obstructive pulmonary disease (COPD) is one of the major diseases threatening human life and health. According to the report released by the World Health Organization (WHO) in 2020, COPD has become the third leading cause of death in the world, featuring a sustainable growth of incidence rate as well as population age. The purpose of this review focuses on the advancement of bioactive natural compounds, such as baicalin, quercetin, resveratrol, and curcumin, which demonstrate promising therapeutic/interventional effects on CODP in vitro and in vivo. Information emphasizing on COPD was systematically collected from several authoritative internet databases including Web of Science, PubMed, Elsevier, Wiley Online Library, and Europe PMC, with a combination of keywords containing "COPD" and "natural small molecular compounds". The new evidence indicated that these valuable molecules featured unique functions in the treatment of COPD through various biological processes such as anti-inflammatory, anti-oxidant, anti-apoptosis, and anti-airway fibrosis. Moreover, we found that the promising effects of these natural compounds on COPD were mainly achieved through JAK3/STAT3/NF-κB and MAPK inflammatory signaling pathways, Nrf2 oxidative stress signaling pathway, and TGF-ß1/Smad 2/3 fibrosis signaling pathway, which referenced to multiple targets like TNF-α, IL-6, IL-8, TIMP-1, MMP, AKT, JAK3, IKK, PI3K, HO-1, MAPK, P38, ERK, etc. Current challenges and future directions in this promising field are also discussed at the end of this review. For the convenience of the readers, this review is divided into ten parts according to the structures of potential natural small molecular compounds. We hope that this review brings a quick look and provides some inspiration for the research of COPD.

[Research progress on therapeutic potential of quercetin].

Quercetin is a naturally occurring phytochemical with good bioactivity, which mainly exists in the form of glycoside in vegetables, fruits, tea, and wine and exhibits beneficial health effects. Quercetin is a dietary polyphenol that exerts the protective effects through diet or use as a food supplement. Compared with chemical agents, quercetin is widely available and safe. Quercetin has been extensively studied for its anti-diabetic, anti-hypertensive, anti-Alzheimer's disease, anti-arthritic, anti-influenza virus, anti-microbial infection, anti-aging, autophagy-regulating, and cardiovascular protective effects. Studies on its activities against different can-cer cell lines have also been reported recently. However, the poor water solubility, rapid in vivo metabolism, and short half-life of quercetin have led to its low bioavailability, thus limiting its application in the field of medicine. Quercetin nanoparticles and nanoparticle drug delivery system have been effectively utilized for enhancing its bioavailability. This paper reviewed the therapeutic potential of quercetin from both preclinical and clinical aspects and proposed solutions to improve its bioavailability, so as to provide a reference for the therapeutic application of natural compounds in the field of medicine.

[Research progress on rutin derivatives].

Compounds derived from natural products present satisfactory efficacy in disease prevention and treatment. The use of chemical substances in plants to promote healthhas increasingly attracted people's attention. Rutin, a typical flavonoid, is mainly found in various vegetables, fruits and Chinese herbal medicines. As a natural antioxidant, it features many pharmacological activities, such as anti-inflammation, anti-virus, anti-tumor, and prevention and treatment of cardiovascular and cerebrovascular diseases. However, the low bioavailability and poor water solubility limit its clinical application. In view of this, its structure is optimized and modified to afford rutin derivatives with good solubility, high bioavailability, stable metabolism and small toxic side effects. So far, a large number of rutin ethers, esters, and complexes have been synthesized and undergone activity testing. This paper reviews the structural modification of rutin in recent years, and the obtained derivatives have excellent properties and significant biological activity.

[Four new lanostane triterpenoids from latex of Euphorbia resinifera].

Four new lanostane triterpenoids, 3ß-hydroxy-12α-methoxylanosta-7,9(11),24-triene(1), 3ß-hydroxy-12α-methoxy-24-methylene-lanost-7,9(11)-dien(2), 3,7-dioxo-lanosta-8,24-diene(3), and 3,7-dioxo-24-methylene-lanost-8-en(4), were isolated from the latex of Euphorbia resinifera with a variety of chromatography methods. Their structures were elucidated based on spectroscopic data and/or comparison with the data reported in previous research. Compounds 1, 2, and 4 showed moderate inhibition of LPS-induced NO production by RAW264.7, with IC_(50) of 30.4, 37.5, and 28.3 µmol·L~(-1), respectively.

Acupuncture therapy on chronic fatigue syndrome based on radar plot: A protocol for an overview of systematic reviews.

BACKGROUND: Chronic fatigue syndrome (CFS) is a debilitating chronic disease of unknown etiology that is recognized by the World Health Organization (WHO) and the United States Center for Disease Control and Prevention (US CDC) as a disorder of the brain. CFS affects 1% (17-24 million people) of the world's population and is a major and costly public health problem. In traditional Chinese medicine (TCM), acupuncture can achieve a certain effect in the treatment of chronic fatigue syndrome, but evidence-based medicine is controversial. This protocol aims to multi-evaluate the literature quality and evidence quality of the current systematic reviews (SRs)/meta-analyses (MAs) of acupuncture treatment for chronic fatigue syndrome, and provide intuitive and reliable evidence synthesis and decision-making basis for clinical treatment. METHODS: Eight databases will be searched from their inception to 1 June, 2020: the Chinese Biomedical Literature Database (CBM), China Science and Technology Journal Database (VIP), China National Knowledge Infrastructure (CNKI), WanFang Database (WF), Web of Science, Embase, PubMed, and Cochrane Library. Published systematic reviews that were reported in Chinese or English, and the included studies were randomized controlled clinical trials (RCTs) for acupuncture in people with CFS will be included. Reviews selection, data extraction and management, and assessment of the study quality will be completed independently by 2 or more reviewers. The quality of evidence, methodological quality, and reporting quality will be evaluated by using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE), A Measurement Tool to Assessment of Multiple Systematic Reviews-2 (AMSTAR-2), Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA), and Adobe Illustrator Creative Cloud (Adobe Illustrator CC) will be used to draw and optimize the radar plot. RESULTS: The article in this overview will be submitted for publication in a peer-reviewed journal. CONCLUSION: We hope to collect evidence from accessible and useful systematic reviews of acupuncture treatment for chronic fatigue syndrome, to provide visual and scientific decision-making methods for more clinical practice and medical research. SYSTEMATIC REVIEW REGISTRATION: INPLASY 202060052.

Impairment of type H vessels by NOX2-mediated endothelial oxidative stress: critical mechanisms and therapeutic targets for bone fragility in streptozotocin-induced type 1 diabetic mice.

Rationale: Mechanisms underlying the compromised bone formation in type 1 diabetes mellitus (T1DM), which causes bone fragility and frequent fractures, remain poorly understood. Recent advances in organ-specific vascular endothelial cells (ECs) identify type H blood vessel injury in the bone, which actively direct osteogenesis, as a possible player. Methods: T1DM was induced in mice by streptozotocin (STZ) injection in two severity degrees. Bony endothelium, the coupling of angiogenesis and osteogenesis, and bone mass quality were evaluated. Insulin, antioxidants, and NADPH oxidase (NOX) inhibitors were administered to diabetic animals to investigate possible mechanisms and design therapeutic strategies. Results: T1DM in mice led to the holistic abnormality of the vascular system in the bone, especially type H vessels, resulting in the uncoupling of angiogenesis and osteogenesis and inhibition of bone formation. The severity of osteopathy was positively related to glycemic levels. These pathological changes were attenuated by early-started, but not late-started, insulin therapy. ECs in diabetic bones showed significantly higher levels of reactive oxygen species (ROS) and NOX 1 and 2. Impairments of bone vessels and bone mass were effectively ameliorated by treatment with anti-oxidants or NOX2 inhibitors, but not by a NOX1/4 inhibitor. GSK2795039 (GSK), a NOX2 inhibitor, significantly supplemented the insulin effect on the diabetic bone. Conclusions: Diabetic osteopathy could be a chronic microvascular complication of T1DM. The impairment of type H vessels by NOX2-mediated endothelial oxidative stress might be an important contributor that can serve as a therapeutic target for T1DM-induced osteopathy.

The Anti-apoptosis Effect of Single Electroacupuncture Treatment via Suppressing Neuronal Autophagy in the Acute Stage of Ischemic Stroke Without Infarct Alleviation.

The main purpose of the study was to investigate the antiapoptotic effect of electroacupuncture (EA) in the acute stage of ischaemic stroke in rats. The cerebral ischemia model was established by middle cerebral artery occlusion (MCAO)/reperfusion in rats. A single EA treatment was performed at the acute stage of ischaemic stroke. The neurological function, brain water content, apoptotic cell number, and cerebral infarct volume were assessed in stroke rats. The expression of autophagy-related proteins (LC3II/I, Beclin1, P62, and LAMP1), Sirtuin 1 (SIRT1), p-JNK, p-ERK1/2, and cleaved caspase-3 (CCAS3) were measured by Western blot, immunofluorescence, and immunohistochemistry. Rapamycin (RAP, an activator of autophagy) was used to confirm the antiapoptotic effect of EA via regulating autophagy. The brain edema infarct size and apoptotic cell number were increasing within 3 days following stroke, and brain edema reached its peak at 24 h after stroke. EA treatment at 24 h after ischaemic stroke obviously suppressed the number of apoptotic cells and brain edema. However, there were no significant differences in infarct volumes among EA-12 h, EA-24 h, and MCAO/R group. Moreover, EA treatment at 24 h after ischaemic stroke obviously suppressed the expression of CCAS3, LC3II/I, Beclin1 while increasing the level of P62 and LAMP1 and hence mediating autophagy, which was reversed by RAP. Meanwhile, the expression of SIRT1, p-ERK1/2, p-JNK were promoted by EA at 24 h after ischaemic stroke. In conclusion, EA treatment may suppress apoptosis possibly via regulating autophagy in the acute period after ischaemic stroke, hence reducing brain injury.

Efficacy and safety of acupuncture in patients with cancer-related fatigue: A protocol for systematic review and meta-analysis.

BACKGROUND: Cancer-related fatigue (CRF) is considered a common complication of cancer or cancer treatment, which has a serious adverse effect on the life and of cancer patients, leading to a decline in their quality of life (QoL). The existing clinical trials revealed that acupuncture has a positive effect on CRF, and there are fewer adverse events confirmed in the corresponding systematic review. However, in recent years, new studies on using acupuncture to treat CRF were conducted, so in order to evaluate its efficacy, an updated systematic review. This protocol provides research methods for systematic review and meta-analysis of the safety and effectiveness of acupuncture for the treatment of CRF. METHODS: We will searched the randomized controlled trial literature of acupuncture treatment for CRF in 4 English and 4 Chinese databases, including PubMed, MEDLINE, Web of Science, Cochrane Central Register of Controlled Trials (Central), China National Knowledge Infrastructure (CNKI), China Biomedical Literature Database(CBM), China Science Journal Database (VIP), and Wanfang Database. Simultaneously, other resources are manually retrieved which include reference lists of identified publications, conference articles, and grey literature. We also included the clinical randomized controlled trials of acupuncture treatment for CRF in the study. The search language is limited to Chinese and English. Two trained reviewers independently completed research screening, data extraction, and research quality assessment. RevMan (V.5.3) software was used to perform data statistical analysis and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to evaluate the quality of evidence. RESULTS: This study is based on past and present clinical evidence to comprehensively evaluate the effectiveness and safety of acupuncture treatment for CRF. CONCLUSION: Through this systematic review, we will provide the latest high-quality evidence of whether acupuncture treatment for CRF is effective and safe and also provide a theoretical basis for clinicians to choose acupuncture for the treatment of CRF. SYSTEMATIC REVIEW REGISTRATION: INPLASY 202090049.

[Research progress on antitumor activity of quercetin derivatives].

Quercetin is a kind of typical flavonoid, mainly found in various vegetables, fruits and Chinese herbs that are consumed daily, with the functions of anti-oxidation, anti-tumor, prevention and treatment of cardiovascular and cerebrovascular diseases. Quercetin is a natural compound with defined anti-tumor activity. Due to its low bioavailability and poor water solubility, quercetin has limitations in clinical application. The quercetin derivatives with good solubility, high bioavailability, metabolic stability, and low toxicity have been obtained through modification of quercetin structure. In recent years, a large number of quercetin ethers, esters, complexes, C-4 carbonyloxy substituted derivatives, A,B-ring modified compounds and other derivatives have been synthesized and tested for in vitro anticancer activity. The quercetin derivatives with anti-tumor activity synthesized in the last 5 years were reviewed in this paper.

Electroacupuncture Inhibits Neuronal Autophagy and Apoptosis via the PI3K/AKT Pathway Following Ischemic Stroke.

Electroacupuncture (EA) is a safe and effective therapy for ischemic stroke in both clinical and laboratory settings. However, the underlying mechanism behind EA treatment for stroke remains unclear. Here, we aimed to evaluate whether EA treatment at the acupoints of Zusanli (ST36) and Quchi (LI11) exerted a neuroprotective effect on ischemic stroke rats by modulating autophagy and apoptosis via the PI3K/AKT/mTOR signaling pathway. EA was performed at 24 h following brain ischemia/reperfusion (I/R) for 30 min per day for 3 days. Our results indicated that EA treatment significantly decreased neurological deficits and cerebral infarct volume in ischemic stroke rats. Also, EA intervention markedly reduced neuronal apoptosis by suppressing the activation of cleaved caspase-3 (CCAS3) at 72 h following I/R, as shown by a Western blot analysis. Furthermore, EA treatment after ischemic stroke suppressed the ischemia activated expression level of LC3II/I and Atg7 and increased the ischemia inhibited expression level of PI3K, phosphorylation of mTOR, phosphorylation of AKT, P62 and LAMP1, hence mediating the autophagy level of the neurocyte, which was reversed by the PI3K inhibitor Dactolisib. In summary, our results indicate that the protective effects of EA treatment at points of Quchi (LI11) and Zusanli (ST36) in rats following cerebral I/R injury was associated with the inhibition of neuronal apoptosis and autophagy via activating the PI3K/AKT/mTOR signaling pathway.