Child ; Humans ; Lead ; Urban Population ; Nutritional Status ; Health Surveys ; China/epidemiology* ; Rural Population

Mammalian target of rapamycin (mTOR) controls cellular anabolism, and mTOR signaling is hyperactive in most cancer cells. As a result, inhibition of mTOR signaling benefits cancer patients. Rapamycin is a US Food and Drug Administration (FDA)-approved drug, a specific mTOR complex 1 (mTORC1) inhibitor, for the treatment of several different types of cancer. However, rapamycin is reported to inhibit cancer growth rather than induce apoptosis. Pyruvate dehydrogenase complex (PDHc) is the gatekeeper for mitochondrial pyruvate oxidation. PDHc inactivation has been observed in a number of cancer cells, and this alteration protects cancer cells from senescence and nicotinamide adenine dinucleotide (NAD^+‍) exhaustion. In this paper, we describe our finding that rapamycin treatment promotes pyruvate dehydrogenase E1 subunit alpha 1 (PDHA1) phosphorylation and leads to PDHc inactivation dependent on mTOR signaling inhibition in cells. This inactivation reduces the sensitivity of cancer cells' response to rapamycin. As a result, rebooting PDHc activity with dichloroacetic acid (DCA), a pyruvate dehydrogenase kinase (PDK) inhibitor, promotes cancer cells' susceptibility to rapamycin treatment in vitro and in vivo.
Humans ; Sirolimus/pharmacology* ; Dichloroacetic Acid/pharmacology* ; Pyruvate Dehydrogenase Complex ; TOR Serine-Threonine Kinases ; Mechanistic Target of Rapamycin Complex 1 ; Neoplasms/drug therapy*

The twenty-first century has already recorded more than ten major epidemics or pandemics of viral disease, including the devastating COVID-19. Novel effective antivirals with broad-spectrum coverage are urgently needed. Herein, we reported a novel broad-spectrum antiviral compound PAC5. Oral administration of PAC5 eliminated HBV cccDNA and reduced the large antigen load in distinct mouse models of HBV infection. Strikingly, oral administration of PAC5 in a hamster model of SARS-CoV-2 omicron (BA.1) infection significantly decreases viral loads and attenuates lung inflammation. Mechanistically, PAC5 binds to a pocket near Asp49 in the RNA recognition motif of hnRNPA2B1. PAC5-bound hnRNPA2B1 is extensively activated and translocated to the cytoplasm where it initiates the TBK1-IRF3 pathway, leading to the production of type I IFNs with antiviral activity. Our results indicate that PAC5 is a novel small-molecule agonist of hnRNPA2B1, which may have a role in dealing with emerging infectious diseases now and in the future.
Animals ; Mice ; Antiviral Agents/pharmacology* ; COVID-19 ; Hepatitis B virus ; Interferon Type I/metabolism* ; SARS-CoV-2/drug effects* ; Heterogeneous-Nuclear Ribonucleoprotein Group A-B/antagonists & inhibitors*

The purpose of this study was to explore the clinical efficacy and safety of Gynostemma pentaphyllum (G. pentaphyllum) in the treatment of hyperlipidemia, and to provide systematic evaluation basis for clinical application. CNKI, Wanfang Data, VIP, Web of science, PubMed, Embase and Cochrane Library were searched for randomized controlled trials (RCTs) about G. pentaphyllum in the treatment of hyperlipidemia. Review Manager 5.4 were used for statistical analysis. Through reading topics, abstracts, and full texts, 27 papers with 2311 cases involved that met the inclusion and exclusion criteria were finally included for the analysis. In terms of curative effect, the effect of G. pentaphyllum alone in increasing high density lipoprotein (HDL) index was better than that of conventional treatment, and the effect of reducing total cholesterol (TC), triglyceride (TG) and low density lipoprotein (LDL) was similar to that of conventional treatment. There was a synergistic effect between G. pentaphyllum and conventional drugs, and the combination of G. pentaphyllum and conventional drugs was superior to conventional treatment in reducing TG and increasing HDL. G. pentaphyllum can also decrease the levels of serum glutamic pyruvic transaminase and glutamic oxaloacetic transaminase in the treatment of hyperlipidemia, indicating a certain protective function of the liver. In terms of safety, there were fewer cases of adverse reactions in the G. pentaphyllum treatment group, and the adverse reaction events reported in the literature was mild. According to the results of meta-analysis, G. pentaphyllum was effective in the treatment of hyperlipidemia, and it has the potential to be combined with traditional drugs, has a certain liver protection function, and was superior to traditional drugs in the treatment of hyperlipidemia.

Background/Aims: Accumulating evidence indicates that L-carnitine (LC) protects against multiorgan damage through its antioxidant properties and preservation of the mitochondria. Little information is available about the effects of LC on renal fibrosis. This study examined whether LC treatment would provide renoprotection in a rat model of unilateral ureteral obstruction (UUO) and in vitro. Methods: Sprague-Dawley rats that underwent UUO were treated daily with LC for 7 or 14 days. The influence of LC on renal injury caused by UUO was evaluated by histopathology, and analysis of gene expression, oxidative stress, mitochondrial function, programmed cell death, and phosphatidylinositol 3-kinase (PI3K)/ AKT/forkhead box protein O 1a (FoxO1a) signaling. In addition, H2O2-exposed human kidney cells (HK-2) were treated with LC. Results: LC treatment inhibited expression of proinflammatory and profibrotic cytokines, and was followed by a significant attenuation of tubulointerstitial inflammation and fibrosis. The increased oxidative stress caused by UUO was associated with mitochondrial dysfunction and excessive apoptosis and autophagy via PI3K/AKT/FoxO1a-dependent signaling, and this was abrogated by administration of LC. In H2O2-exposed HK-2 cells, LC decreased intracellular production of reactive oxygen species, and suppressed expression of profibrotic cytokines and reduced the number of apoptotic cells. Conclusions LC protects against the progression of tubulointerstitial fibrosis in an obstructed kidney.

BACKGROUND/AIMS: Evidence suggests that Shen-Kang (SK), a traditional Chinese herbal medicine, protects against various types of renal injury. In this study, we evaluated whether SK treatment confers renoprotection in a rat model of chronic tacrolimus (TAC) nephropathy. METHODS: Rats were treated daily with TAC (1.5mg/kg, subcutaneously) and SK (450 mg/kg, intravenously) for 4 weeks. The effects of SK on TAC-induced renal injury were assessed by measuring renal function, urine albumin excretion, histopathology, inflammatory cell infiltration, expression of profibrotic (transforming growth factor β1 [TGF-β1] and TGF-β inducible gene-h3 [βig-h3]) and proinflammatory cytokines, oxidative stress, and apoptotic cell death. RESULTS: Administration of SK preserved glomerular integrity (fractional mesangial area and Wilms tumor 1-positive glomeruli), attenuated tubulointerstitial fibrosis, and reduced the number of ectodermal dysplasia 1-positive cells, and this was paralleled by improved urine albumin excretion and renal dysfunction. At the molecular level, SK treatment suppressed expression of TGF-β1/Smad2/3, βig-h3, and proinflammatory cytokines. Oxidative stress and apoptotic cell death were significantly decreased with SK treatment, and apoptosis-related genes were regulated toward cell survival (active caspase-3 and the B-cell lymphoma-2/Bcl2-associated X [Bcl-2/Bax] ratio). CONCLUSIONS SK protects against TAC-induced renal injury.

AIM: To investigate the effects of baicalein(BAI)on the proliferation and migration of gastric cancer MGC-803 cells and the mechanisms.METHODS:After MGC-803 cells were treated with BAI at different concen-trations,the viability of the MGC-803 cells was tested by MTT assay.The cell colony formation ability were detected by plate colony formation assay.Wound-healing and Transwell cell migration assays were used to test the migration ability of the MGC-803 cells.The concentration of 12-hydroxyeicosatetraenoic acid(12-HETE)was measured by ELISA.The pro-tein levels of platelet type 12-lipoxygenase(p12-LOX),vascular endothelial growth factor(VEGF),p-ezrin and epithelial-mesenchymal transition(EMT)markers in MGC-803 cells were determined by Western blot.RESULTS:BAI significantly inhibited the proliferation,plate colony formation and migration abilities of the MGC-803 cells(P<0.05 or P<0.01), down-regulated the concentration of p12-LOX metabolite 12-HETE significantly(P<0.05 or P<0.01), decreased the protein levels of p12-LOX,VEGF,p-ezrin,vimentin and Snail(P<0.05 or P<0.01),and increased the protein expres-sion of E-cadherin(P<0.01).CONCLUSION:BAI suppresses the proliferation and migration abilities of gastric cancer MGC-803 cells effectively.These effects of BAI may be related to regulating the protein levels of p12-LOX,VEGF,p-ezrin and EMT-related proteins.

Ankylosing spondylitis has become a common disease, whether early stage of the low back pain or disability of the late stage of the disease has a serious impact on life quality. There is an urgent need of safe and effective treatment to treat the disease. This article introduced two cases of ankylosing spondylitis treated by modified Jingang Pills, with significant efficacy.

Objective To observe the clinical effect of Xingnaojing injection combined with naloxone in the treatment of hypoxic ischemic encephalopathy.Methods 62 patients with hypoxia ischemia encephalopathy were randomly assigned into the control group(31 cases)and the treatment group(31 cases).The control group used naloxone treatment on the basis of the conventional treatment.The treatment group received Xingnaojing injection combined with naloxone treatment on the basis of routine treatment.The changes in different time of Glasgow Coma Scale(GCS) scores of the two groups after treatment were compared.Results After treatment for 1 ,5,1 0,1 5d,the GCS scores in the control group were (5.27 ±0.87)points,(9.03 ±0.72)points,(1 0.03 ±0.72)points,(1 3.03 ±0.72)points respectively,which in the treatment group were (5.1 4 ±1 .03)points,(9.24 ±1 .06)points,(1 3.31 ±2.83)points, (15.31 ±0.93)points.The differences of GCS scores after treatment for 15,10d between the two groups were statistically significant(t =1 5.1 1 3,1 0.501 ,P =0.00,0.00).In the control group,the total effective rate was 50.0%,which of the treatment group was 82.7%,the total effective rate between the two groups had statistically significant difference (χ2 =6.437,P <0.05).Conclusion On the basis of routine treatment,Xingnaojing injection combined with naloxone in the treatment of hypoxic ischemic encephalopathy has better effect than the single use of naloxone treatment.