Comparison of a Hemostatic Powder and Standard Treatment in the Control of Active Bleeding From Upper Nonvariceal Lesions : A Multicenter, Noninferiority, Randomized Trial.

BACKGROUND: The effectiveness of the hemostatic powder TC-325 as a single endoscopic treatment for acute nonvariceal upper gastrointestinal bleeding is uncertain. OBJECTIVE: To compare TC-325 with standard endoscopic hemostatic treatments in the control of active bleeding from nonvariceal upper gastrointestinal causes. DESIGN: One-sided, noninferiority, randomized, controlled trial. (ClinicalTrials.gov: NCT02534571). SETTING: University teaching hospitals in the Asia-Pacific region. PATIENTS: 224 adult patients with acute bleeding from a nonvariceal cause on upper gastrointestinal endoscopy. INTERVENTION: TC-325 (n = 111) or standard hemostatic treatment (n = 113). MEASUREMENTS: The primary outcome was control of bleeding within 30 days. Other outcomes included failure to control bleeding during index endoscopy, recurrent bleeding after initial hemostasis, further interventions, blood transfusion, hospitalization, and death. RESULTS: 224 patients were enrolled (136 with gastroduodenal ulcers [60.7%], 33 with tumors [14.7%], and 55 with other causes of bleeding [24.6%]). Bleeding was controlled within 30 days in 100 of 111 patients (90.1%) in the TC-325 group and 92 of 113 (81.4%) in the standard treatment group (risk difference, 8.7 percentage points [1-sided 95% CI, 0.95 percentage point]). There were fewer failures of hemostasis during index endoscopy with TC-325 (3 [2.7%] vs. 11 [9.7%]; odds ratio, 0.26 [CI, 0.07 to 0.95]). Recurrent bleeding within 30 days did not differ between groups (9 [8.1%] vs. 10 [8.8%]). The need for further interventions also did not differ between groups (further endoscopic treatment: 8 [7.2%] vs. 10 [8.8%]; angiography: 2 [1.8%] vs. 4 [3.5%]; surgery: 1 [0.9%] vs. 0). There were 14 deaths in each group (12.6% vs. 12.4%). LIMITATION: Clinicians were not blinded to treatment. CONCLUSION: TC-325 is not inferior to standard treatment in the endoscopic control of bleeding from nonvariceal upper gastrointestinal causes. PRIMARY FUNDING SOURCE: General Research Fund to the University Grants Committee, Hong Kong SAR Government.

Comparative study on fecal flora and blood biochemical indexes in normal and diarrhea British Shorthair cats.

In recent years, 16S ribosomal DNA (16S rDNA) sequencing has been widely developed. In the present study, we investigated the changes of fecal flora analyzed by sequencing of 16S rDNA and the alteration of blood biochemical indexes in cats during diarrhea. Seven normal fecal samples and seven fecal samples of British Shorthair cats with bacterial diarrhea about 6 months old were collected. The 16S rDNA V3 region of the bacteria was amplified for high-throughput sequencing. Finally, species analysis at various levels was performed. At the same time, samples of blood were taken to examine the changes of biochemical indexes in cats with diarrhea. The abundance and diversity of microflora in the healthy group were greater than those in the diarrhea group. The normal floras in the feces of healthy cats were Firmicutes, Actinobacteria, Bacteroidetes and Proteobacteria. The content of Proteobacteria and Firmicutes varied greatly in diarrheal cats. In addition, the number of white blood cells, lymphocytes, neutrophils, and globulin were increased in cats with diarrhea, whereas albumin level was decreased in diarrheal cats. In conclusion, the present study suggests 16SrDNA technology showed that the intestinal Proteus was abundant, and the content of Firmicutes was scarce in cats with diarrhea. Escherichia-Shigella was the main pathogens in this sample. Rapid blood biochemical tests may help clinicians to assess the severity and prognosis of cats with diarrhea.

Fate of Fat Grafting In Vivo and In Vitro: Does the Suction-Assisted Lipectomy Device Matter?

BACKGROUND: Recently, there has been increasing research interest in identifying the effect of liposuction procedures on fat graft survival in order to clarify whether different harvest techniques affect the quality of fat grafts. OBJECTIVES: The aim of this study was to investigate the effect of 2 liposuction methods on the survival and regeneration potential of grafted fat tissue. The proliferation and differentiation potentials of adipose-derived stem cells (ASCs) isolated by both methods was also investigated. METHODS: Fat grafts were collected from patients who underwent liposuction procedures by 2 different methods: traditional suction-assisted liposuction (TSAL) and vibration amplification of sound energy at resonance (VASER). One portion of the lipoaspirates was implanted into the subcutaneous layer of nu mice for 4 and 12 weeks. ASCs were isolated from the other portion of the lipoaspirate and subjected to proliferation and differentiation assays. RESULTS: Although in vivo fat grafting presented similar adipose tissue survival for the 2 different liposuction methods, more angiogenesis and less fibrosis was observed in the VASER group based on histologic evaluation. Furthermore, VASER-derived ASCs presented better quality in terms of cell differentiation capacity. CONCLUSIONS: The in vivo study confirmed better graft angiogenesis with less inflammation, apoptosis, and scar formation in the VASER group. ASCs harvested with VASER exhibited increased differentiation capacity compared with those obtained by TSAL, and represent an excellent source for fat grafting and regenerative medicine.

Effects of Preoperative Isokinetic Eccentric Training and Whey Protein Isolate Supplement on Quadriceps Strength and Knee Function in Patients with Anterior Cruciate Ligament Rupture.

Objective To explore the effect of preoperative isokinetic eccentric training with or not whey protein isolate supplement before operation on lower limb muscle strength and knee function in patients with anterior cruciate ligament (ACL) rupture. Methods A total of 22 male volunteers aged 18-40 years with ACL rupture were recruited in outpatient service. With randomized block design,subjects were randomly assigned to isokinetic eccentric training (IE) group and isokinetic eccentric training with whey protein isolate supplement (IE+WPI) group. The IE group received isokinetic eccentric training of the injured limb on an isokinetic dynamometer under the guidance of physiatrist in laboratory before operation. There were 3-4 sets per day with 8-10 repetitions for each set,twice a week,with at least one day between sessions. The IE+WPI group were supplied with whey protein isolate 22 g per day on the basis of isokinetic eccentric training,taking breakfast or 30-60 minutes after the training. The intervention lasted for 6 weeks. Isokinetic muscle strength of limbs,the function and laxity of knee,the circumferences of thigh and knee,and the body composition were measured before and after the treatment. Results Compared with baseline,the peak torque (PT) of isokinetic-eccentric contraction (IE group:41.0%,P=0.018;IE+WPI group:46.7%,P=0.008) and the concentric contraction (IE group:29.6%,P=0.018;IE+WPI group:38.9%,P=0.038) of quadriceps in the two training groups significantly increased after isokinetic eccentric training. The Lysholm score increased significantly in IE+WPI group compared with baseline (P=0.018). Conclusions Isokinetic eccentric training before operation for ACL rupture patients can increase the strength of quadriceps and improve the function of knees. Protein isolate supplement can improve such effect.

[Effect of anterior cruciate ligament rupture on hamstring: quadriceps ratio during isokinetic knee extension and flexion at 30 degrees of flexion].

OBJECTIVE: To evaluate the change in hamstring (H):quadriceps (Q) ratio following anterior cruciate ligament (ACL) rupture during isokinetic knee extension and flexion at 30 degrees of flexion which is important for knee dynamic function. METHODS: A study was performed in 25 male complete unilateral ACL ruptures. Isokinetic concentric and eccentric quadriceps and hamstring muscle tests in both the deficient knees and intact knees were performed at 60°/s, respectively. At 30 degrees of flexion, the average torque of quadriceps and hamstring, Qe:Qc ratios (ratios of eccentric quadriceps to concentric quadriceps muscle torque), He:Hc ratios (eccentric hamstring to concentric hamstring), Hc:Qc ratios (concentric hamstring to concentric quadriceps), He:Qc ratios (eccentric hamstring to concentric quadriceps), and Hc:Qe ratios (concentric hamstring to eccentric quadriceps) were calculated. Wilcoxon matched-pairs signed-ranks test was used. RESULTS: At 30 degrees of knee flexion, a significant reduction (P<0.05) in the average torque of quadriceps was observed at concentric and eccentric 60°/s produced by the deficient-side compared with the intact side. In addition, Hc:Qc, He:Qc, and Qe:Qc significantly increased on the ACL-deficient side. CONCLUSION: The change in H :Q ratio in the mode of isokinetic 60°/s at 30 degrees of knee flexion might therefore be a new tool to objectively document muscle function in ACL-deficient knee.

An internet-based epidemiological investigation of the outbreak of H7N9 Avian influenza A in China since early 2013.

BACKGROUND: In early 2013, a new type of avian influenza, H7N9, emerged in China. It quickly became an issue of great public concern and a widely discussed topic on the Internet. A considerable volume of relevant information was made publicly available on the Internet through various sources. OBJECTIVE: This study aimed to describe the outbreak of H7N9 in China based on data openly available on the Internet and to validate our investigation by comparing our findings with a well-conducted conventional field epidemiologic study. METHODS: We searched publicly accessible Internet data on the H7N9 outbreak primarily from government and major mass media websites in China up to February 10, 2014. Two researchers independently extracted, compared, and confirmed the information of each confirmed H7N9 case using a self-designed data extraction form. We summarized the epidemiological and clinical characteristics of confirmed H7N9 cases and compared them with those from the field study. RESULTS: According to our data updated until February 10, 2014, 334 confirmed H7N9 cases were identified. The median age was 58 years and 67.0% (219/327) were males. Cases were reported in 15 regions in China. Five family clusters were found. Of the 16.8% (56/334) of the cases with relevant data, 69.6% (39/56) reported a history of exposure to animals. Of the 1751 persons with a close contact with a confirmed case, 0.6% (11/1751) of them developed respiratory symptoms during the 7-day surveillance period. In the 97.9% (327/334) of the cases with relevant data, 21.7% (71/327) died, 20.8% (68/327) were discharged from a hospital, and 57.5% (188/327) were of uncertain status. We compared our findings before February 10, 2014 and those before December 1, 2013 with those from the conventional field study, which had the latter cutoff date of ours in data collection. Our study showed most epidemiological and clinical characteristics were similar to those in the field study, except for case fatality (71/327, 21.7% for our data before February 10; 45/138, 32.6% for our data before December 1; 47/139, 33.8% for the field study), time from illness onset to first medical care (4 days, 3 days, and 1 day), and time from illness onset to death (16.5 days, 17 days, and 21 days). CONCLUSIONS: Findings from our Internet-based investigation were similar to those from the conventional field study in most epidemiological and clinical aspects of the outbreak. Importantly, publicly available Internet data are open to any interested researchers and can thus greatly facilitate the investigation and control of such outbreaks. With improved efforts for Internet data provision, Internet-based investigation has a great potential to become a quick, economical, novel approach to investigating sudden issues of great public concern that involve a relatively small number of cases like this H7N9 outbreak.

The role and mechanism of pyroptosis and potential therapeutic targets in non-alcoholic fatty liver disease (NAFLD).

Non-alcoholic fatty liver disease (NAFLD) is a clinical pathological syndrome characterized by the excessive accumulation of fat within liver cells, which can progress to end-stage liver disease in severe cases, posing a threat to life. Pyroptosis is a distinct, pro-inflammatory form of cell death, differing from traditional apoptosis. In recent years, there has been growing research interest in the association between pyroptosis and NAFLD, encompassing the mechanisms and functions of pyroptosis in the progression of NAFLD, as well as potential therapeutic targets. Controlled pyroptosis can activate immune cells, eliciting host immune responses to shield the body from harm. However, undue activation of pyroptosis may worsen inflammatory responses, induce cellular or tissue damage, disrupt immune responses, and potentially impact liver function. This review elucidates the involvement of pyroptosis and key molecular players, including NOD-like receptor thermal protein domain associated protein 3(NLRP3) inflammasome, gasdermin D (GSDMD), and the caspase family, in the pathogenesis and progression of NAFLD. It emphasizes the promising prospects of targeting pyroptosis as a therapeutic approach for NAFLD and offers valuable insights into future directions in the field of NAFLD treatment.

Current insight on the mechanisms of programmed cell death in sepsis-induced myocardial dysfunction.

Sepsis is a clinical syndrome characterized by a dysregulated host response to infection, leading to life-threatening organ dysfunction. It is a high-fatality condition associated with a complex interplay of immune and inflammatory responses that can cause severe harm to vital organs. Sepsis-induced myocardial injury (SIMI), as a severe complication of sepsis, significantly affects the prognosis of septic patients and shortens their survival time. For the sake of better administrating hospitalized patients with sepsis, it is necessary to understand the specific mechanisms of SIMI. To date, multiple studies have shown that programmed cell death (PCD) may play an essential role in myocardial injury in sepsis, offering new strategies and insights for the therapeutic aspects of SIMI. This review aims to elucidate the role of cardiomyocyte's programmed death in the pathophysiological mechanisms of SIMI, with a particular focus on the classical pathways, key molecules, and signaling transduction of PCD. It will explore the role of the cross-interaction between different patterns of PCD in SIMI, providing a new theoretical basis for multi-target treatments for SIMI.

Anthelmintic nitazoxanide protects against experimental pulmonary fibrosis.

BACKGROUND AND PURPOSE: Nitazoxanide is a therapeutic anthelmintic drug. Our previous studies found that nitazoxanide and its metabolite tizoxanide activated adenosine 5'-monophosphate-activated protein kinase (AMPK) and inhibited signal transducer and activator of transcription 3 (STAT3) signals. As AMPK activation and/or STAT3 inhibition are targets for treating pulmonary fibrosis, we hypothesized that nitazoxanide would be effective in experimental pulmonary fibrosis. EXPERIMENTAL APPROACH: The mitochondrial oxygen consumption rate of cells was measured by using the high-resolution respirometry system Oxygraph-2K. The mitochondrial membrane potential of cells was evaluated by tetramethyl rhodamine methyl ester (TMRM) staining. The target protein levels were measured by using western blotting. The mice pulmonary fibrosis model was established through intratracheal instillation of bleomycin. The examination of the lung tissues changes were carried out using haematoxylin and eosin (H&E), and Masson staining. KEY RESULTS: Nitazoxanide and tizoxanide activated AMPK and inhibited STAT3 signalling in human lung fibroblast cells (MRC-5 cells). Nitazoxanide and tizoxanide inhibited transforming growth factor-ß1 (TGF-ß1)-induced proliferation and migration of MRC-5 cells, collagen-I and α-smooth muscle cell actin (α-SMA) expression, and collagen-I secretion from MRC-5 cells. Nitazoxanide and tizoxanide inhibited epithelial-mesenchymal transition (EMT) and inhibited TGF-ß1-induced Smad2/3 activation in mouse lung epithelial cells (MLE-12 cells). Oral administration of nitazoxanide reduced the bleomycin-induced mice pulmonary fibrosis and, in the established bleomycin-induced mice, pulmonary fibrosis. Delayed nitazoxanide treatment attenuated the fibrosis progression. CONCLUSIONS AND IMPLICATIONS: Nitazoxanide improves the bleomycin-induced pulmonary fibrosis in mice, suggesting a potential application of nitazoxanide for pulmonary fibrosis treatment in the clinic.

Sequential treatment for diabetic foot ulcers in dialysis patients: A case report.

BACKGROUND: Diabetic foot ulcers (DFUs) are common in patients with diabetes, especially those undergoing hemodialysis. In severe cases, these ulcers can cause damage to the lower extremities and lead to amputation. Traditional treatments such as flap transposition and transfemoral amputation are not always applicable in all cases. Therefore, there is a need for alternative treatment methods. CASE SUMMARY: This report describes a 62-year-old female patient who was admitted to the hospital with plantar and heel ulcers on her left foot. The patient had a history of renal failure and was undergoing regular hemodialysis. Digital subtraction angiography showed extensive stenosis and occlusion in the left superficial femoral artery, left peroneal artery and left posterior tibial artery. Following evaluation by a multidisciplinary team, the patient was diagnosed with type 2 DFUs (TEXAS 4D). Traditional treatments were deemed unsuitable, and the patient was treated with endovascular surgery in the affected area, in addition to supportive medical treatment, local debridement, and sequential repair using split-thickness skin and tissue-engineered skin grafts combined with negative pressure treatment. After four months, the wound had completely healed, and the patient was able to walk with a walking aid. CONCLUSION: This study demonstrates a new treatment method for DFUs was successful, using angioplasty, skin grafts, and negative pressure.

The insulin long-acting chitosan - Polyethyleneimine nanoparticles to treat the type 2 diabetes mellitus and prevent the associated complications.

Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder, which is ultimately treated by the insulin (INS). However, the subcutaneous (s. c.) injection of insulin solution faces the problems of pain and unsatisfactory patient compliance. In this study, the long-acting formulations of insulin are propsed to treat the T2DM and prevent the associated complications. The chitosan (CS) and/or branched polyethyleneimine (bPEI) nanoparticles (bPEI-INS NPs, CS-bPEI-INS NPs) were constructed to load insulin. The long -acting nanoparticles successfully achieved the sustained release of the INS in vitro and in vivo. After s. c. administration, the CS-bPEI-INS NPs greatly improved the INS bioavailability. As a result, the CS-bPEI-INS NPs produced sustained glucose-lowering effects, promising short-term and long-term hypoglycemic efficacy in the T2DM model. Furthermore, the treatment of the CS-bPEI-INS NPs greatly protected the islet in the pancreas and prevented the associated complications of the T2DM, such as cardiac fibrosis in the myocardial interstitium and the perivascular area. In a word, the CS-bPEI-INS NPs was an encouraging long-acting formulation of insulin and had great potential in the treatment of T2DM.

Activatable unsaturated liposomes increase lipid peroxide of cell membrane and inhibit tumor growth.

The cancer chemodynamic therapy based on the Fenton reaction has been attracting more and more attention. However, the performance of the Fenton reaction is restricted by the unsuitable physiological pH value and inadequate H2O2 content in the tumor microenvironment (TME). In this study, we proposed a novel method of inducing lipid peroxide (LPO) of the cancer cell membrane, whose performance is not limited by the pH value and H2O2 in the TME. The activatable LPO-inducing liposomes were constructed by encapsulating Fe3+-containing compound ferric ammonium citrate (FC) in the unsaturated soybean phospholipids (SPC). It was found that the FC could be reduced by the overexpressed glutathione (GSH) in the TME and produce iron redox couple. The Fe3+/Fe2+ mediated the peroxidation of the unsaturated SPC and induced the LPO in the cancer cells. Finally, LPO accumulation led to cancer cell death and tumor growth inhibition. Furthermore, the activatable liposomes did not damage healthy tissues because of the low GSH content in normal tissues and the GSH-triggered activation of the nanocarrier. Together, our findings revealed that FC-SPC-lipo displayed excellent anti-tumor performance and its therapeutic effects are less influenced by the TME, compared with the traditional ferroptosis.

Repurposing nitazoxanide as a novel anti-atherosclerotic drug based on mitochondrial uncoupling mechanisms.

BACKGROUND AND PURPOSE: The anthelmintic drug nitazoxanide has a mitochondrial uncoupling effect. Mitochondrial uncouplers have been proven to inhibit smooth muscle cell proliferation and migration, inhibit NLRP3 inflammasome activation of macrophages and improve dyslipidaemia. Therefore, we aimed to demonstrate that nitazoxanide would protect against atherosclerosis. EXPERIMENTAL APPROACH: The mitochondrial oxygen consumption of cells was measured by using the high-resolution respirometry system, Oxygraph-2K. The proliferation and migration of A10 cells were measured by using Edu immunofluorescence staining, wound-induced migration and the Boyden chamber assay. Protein levels were measured by using the western blot technique. ApoE (-/-) mice were fed with a Western diet to establish an atherosclerotic model in vivo. KEY RESULTS: The in vitro experiments showed that nitazoxanide and tizoxanide had a mitochondrial uncoupling effect and activated cellular AMPK. Nitazoxanide and tizoxanide inhibited serum- and PDGF-induced proliferation and migration of A10 cells. Nitazoxanide and tizoxanide inhibited NLRP3 inflammasome activation in RAW264.7 macrophages, the mechanism by which involved the AMPK/IκBα/NF-κB pathway. Nitazoxanide and tizoxanide also induced autophagy in A10 cells and RAW264.7 macrophages. The in vivo experiments demonstrated that oral administration of nitazoxanide reduced the increase in serum IL-1ß and IL-6 levels and suppressed atherosclerosis in Western diet-fed ApoE (-/-) mice. CONCLUSION AND IMPLICATIONS: Nitazoxanide inhibits the formation of atherosclerotic plaques in ApoE (-/-) mice fed on a Western diet. In view of nitazoxanide being an antiprotozoal drug already approved by the FDA, we propose it as a novel anti-atherosclerotic drug with clinical translational potential.

Bie-Jia-Ruan-Mai-Tang, a Chinese Medicine Formula, Inhibits Retinal Neovascularization in Diabetic Mice Through Inducing the Apoptosis of Retinal Vascular Endothelial Cells.

Proliferative diabetic retinopathy (PDR) is one of the main complications of diabetes, mainly caused by the aberrant proliferation of retinal vascular endothelial cells and the formation of new blood vessels. Traditional Chinese medicines possess great potential in the prevention and treatment of PDR. Bie-Jia-Ruan-Mai-Tang (BJ), a Chinese medicine formula, has a good therapeutic effect on PDR clinically; however, the mechanism of action involved remains unclear. Therefore, we investigated the effect of BJ on PDR through in vitro and in vivo experiments. A diabetic mouse model with PDR was established by feeding a high-fat-high-glucose diet combined with an intraperitoneal injection of streptozotocin (STZ), while high-glucose-exposed human retinal capillary endothelial cells (HRCECs) were employed to mimic PDR in vitro. The in vivo experiments indicated that BJ inhibited the formation of acellular capillaries, decreased the expression of VEGF, and increased the level of ZO-1 in diabetic mice retina. In vitro experiments showed that high glucose significantly promoted cell viability and proliferation. However, BJ inhibited cell proliferation by cycle arrest in the S phase, thus leading to apoptosis; it also increased the production of ROS, decreased the mitochondrial membrane potential, reduced the ATP production, and also reduced the expressions of p-PI3K, p-AKT, and Bcl-xL, but increased the expressions of Bax and p-NF-κB. These results suggest that BJ induces the apoptosis of HRCECs exposed to high glucose through activating the mitochondrial death pathway by decreasing the PI3K/AKT signaling and increasing the NF-κB signaling to inhibit the formation of acellular capillaries in the retina, thus impeding the development of PDR.

Neolignans and Diarylheptanoids with Anti-Inflammatory Activity from the Rhizomes of Alpinia zerumbet.

The dried leaves and rhizomes of Alpinia zerumbet have been traditionally used as food and medicine. Anti-inflammatory activity-guided phytochemical investigation into the rhizomes of A. zerumbet led to the isolation of 17 compounds including 10 neolignans (1-10, 1a, 1b, 2a, 2b, 3a, 3b, 4, and 5 are new compounds) and seven diarylheptanoids (11-17) in which 1-3 were three pairs of enantiomers. 4 was only one enantiomer and 5 was a racemic mixture. Compounds 1a, 1b, 2a, and 2b incorporated an 8',9'-dinorneolignan skeleton, which was rare in the lignan family. The planar structures of these compounds were elucidated by extensive analyses of spectroscopic data. The relative and absolute configurations were determined by the time-dependent density functional theory (TDDFT)-based electronic circular dichroism (ECD) calculation method. The 95% ethanol extract and ethyl acetate extract of A. zerumbet were found to show anti-inflammatory activity against croton oil-induced ear edema in mice with inhibition rates of 20.0 and 47.6% at a dose of 80 mg/kg, respectively. Bioassays showed that compounds 1a, 1b, 2a, 2b, and 12 moderately inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW264.7 cells with IC50 values of 3.62, 7.63, 6.51, 5.60, and 8.33 µM, respectively.

Hu-Zhang-Qing-Mai-Yin Inhibits Proliferation of Human Retinal Capillary Endothelial Cells Exposed to High Glucose.

BACKGROUND: Diabetic retinopathy (DR) is one of the serious complications of diabetes and an important cause of blindness. Despite much research on the pathogenesis of DR, there is still a lack of safe and effective treatment methods. Hu-zhang-qing-mai-yin (HZQMY), a Chinese medicine formula, has been clinically used in the safe and effective treatment of DR for many years. However, the systematic pharmacological research is lacking. The aim of this study was to evaluate the anti-DR effects of HZQMY and explore the possible mechanism involved. METHODS: The constituents of HZQMY were analyzed by LC-MS/MS. DR model was established by high glucose simulation on human retinal capillary endothelial cells (HRCECs) in vitro. The cell viability, cell proliferation, cell apoptosis, and tube formation were assessed. Subsequently the related mechanisms were analyzed by assays for JC-1 mitochondrial membrane potential (MMP), intracellular ROS, ATP, western blot and proteomics. RESULTS: 27 main chemical components contained in HZQMY were identified. HZQMY significantly inhibited the viability and proliferation of HRCECs exposed to high glucose, and promoted the apoptosis. In addition, HZQMY also boosted the release of ROS and suppressed tube formation of HRCECs under high glucose exposure. Meanwhile, HRCECs treated with high glucose released more ROS than normal cells, which could be markedly inhibited by HZQMY in a dose-dependent manner. Additionally, western blot assay indicated that HZQMY increased the expression of proteins related to the P38 signaling pathway and inhibited nuclear factor kappa-B (NF-κB) pathway. Proteomic analysis predicted that HSPA4, MAPK3, ENO1, EEF2 and ERPS may be the candidate targets of HZQMY in HRCECs. CONCLUSIONS: HZQMY inhibited the proliferation and promoted the Mitochondria related apoptosis of HRCECs exposed to high glucose possibly through regulating P38 and NF-κB signaling pathway.

Aidi injection induces apoptosis of hepatocellular carcinoma cells through the mitochondrial pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The incidence and mortality rates of hepatocellular carcinoma are very high all over the world, which seriously threatens human life and health. Aidi injection as a Chinese medicine preparation has a positive curative effect on hepatocellular carcinoma, but its mechanism remains unclear. AIM OF THE STUDY: The purpose of this study is to evaluate the anti-hepatocellular carcinoma effects of Aidi injection and explore its mechanism of action vitro and vivo. MATERIALS AND METHODS: The main components of Aidi injection were determined by LC-MS/MS. The effects of Aidi injection on the viability of HepG2 and PLC/PRF/5 cells were detected via CCK-8 analysis and Calcein AM/PI staining. DAPI staining and flow cytometry were applied to analyze the apoptosis-induced effects of Aidi injection on hepatocellular carcinoma cells (HCCs). The growth inhibition of Aidi injection on hepatocellular carcinoma was observed in nude mice bearing PLC/PRF/5 cells. The related signal transduction and apoptosis pathways were investigated through assays for JC-1 mitochondrial membrane potential (MMP), RNA-seq, KEGG, PPI and WB. RESULTS: There were 12 main chemical components contained in Aidi injection, viz. cantharidin, syringin, calycosin-7-o-ß-Dglucoside, isozinpidine, ginsenosides Rd, Rc, Rb1, Re, and Rg1, astragalosides II and IV, and eleutheroside E. Aidi injection significantly inhibited the proliferation of HepG2 and PLC/PLF/5 cells with IC50 of 20.66 mg/ml and 27.5 mg/ml at 48h, respectively, increased the proportion of dead cells, induced cell apoptosis, suppressed the tumor growth of nude mice bearing PLC/PLF/5 cells, reduced MMP, activated PI3K/Akt and MAPK signal transduction pathways, down-regulated the expression of p-PI3K and Bcl-xL, and up-regulated the expression of p-JNK, p-p38 and Bim. CONCLUSION: Aidi injection inhibits the growth of liver cancer probably through regulating PI3K/Akt and MAPK signal transduction pathways, inducing MMP collapse to activate the mitochondrial apoptosis pathway, and then eliciting apoptosis of HCCs.

[Spatial Variability and Contamination of Arsenic in Soils of Xijiang River Basin].

In this study, 2585 soil samples were collected in the Xijiang River Basin in Guangxi Zhuang Autonomous Region and the spatial variability and contamination of Arsenic in soils were evaluated using geostatistical and GIS tools. The results showed that the concentrations of As in surface soils (23.82 mg·kg-1) were higher than the background values of the Guangxi and Xijiang Rivers in natural soils; the upstream values (Diaojiang River and Huanjiang River) (30.22 mg·kg-1) were significantly higher than those in other regions. Concentrations of As in soil samples were in the order of soil in mining areas > soil in dryland > natural soil > paddy soil. As in mining areas were significantly higher than in other areas; high As concentrations were measured in the upstream of the Diaojiang River basin and the downstream of the Huanjiang River Basin. Low concentration clusters were in the six villages of Nandan, which are far from the mine, and in the upper reaches of the Dahuanjiang River and Xiaohuanjiang River Basin. Spatial autocorrelations of arsenic in the watershed soil were evident and the structural variability was dominant. The concentration of As in the upper reaches decreased from the northwest to the southeast. High As concentrations were distributed naturally along the river basin; concentrations in the middle and lower reaches of the basin were between 0.44 mg·kg-1 and 40 mg·kg-1. The concentration levels of As in total soil samples ranged from no-pollution to slight pollution, and the pollution was mainly distributed in the administrative areas of the city and the intensive areas of mining activities, among which the soil pollution in Jinchengjiang River and Nandan counties was more prominent. Effective measures should be taken to strengthen the safety level of tailings reservoirs during the rainy season, so as to maintain the production levels while protecting living standards of local residents.

[Concentrations and Health Risk Assessments of Heavy Metal Contents in Soil and Rice of Mine Contaminated Areas].

Nandan County is famous for its mining of nonferrous metals. In order to investigate the effects of mining activities on the soil and rice and to evaluate the health risk of the exposure of typical local inhabitants to heavy metals via consumption of rice, a consecutive 3-day household diet survey in four villages in Nandan was conducted. Liuzhai is an uncontaminated contrast area, and Chehe, Dachang, and Zhanglao are contaminated areas. The data for rice consumption rates were obtained. At the same time, 56 soil samples from rice fields and 90 rice samples were collected for the analysis of As, Sb, Cd, Pb, Cu, and Zn. In addition, the potential health risk of the exposure of local people to heavy metals via consumption of the rice was assessed using the pollution index method and the data from the intake of heavy metals. Results showed that the mean contents of As, Sb, Cd, Pb, Cu, and Zn were 58.1, 16.4, 1.22, 49.1, 52.1, and 271 mg·kg-1 in the soil samples from contaminated areas, with higher pollution risks than from the control area for soil heavy metal contents. The Nemero comprehensive contamination index (PN) was 3.14, a heavy pollution grade. Cd contents in rice in Liuzhai, Chehe, Dachang, and Zhanglao were 2.23 times, 4.40 times, 3.81 times, and 3.52 times higher than those of GB 2762-2017.The content in rice exceeds the standard in all four areas. The daily intake (DI) of Cd in the four areas was higher than the provisional tolerable daily intake (PTDI) established by FAO/WHO. This indicates that Cd and As are the major heavy metal elements posing health risks to the health of the inhabitants in the mining areas and that the inhabitants in the mining areas are facing severe risks of exposure to heavy metals.