Essential role of monocytes and macrophages in the progression of acute pancreatitis

Acute pancreatitis(AP) is an inflammatory condition of the pancreas caused by an imbalance in factors involved in maintaining cellular homeostasis.Earliest events in AP occur within acinar cells accompanied by other principal contributors to the inflammatory response i.e.the endothelial cells,immunocytes(granulocytes,monocytes/macrophages,lymphocytes) and neutrophils.Monocytes/macrophages are important inflammatory mediators,involved in the pathophysiology of AP,known to reside in the peritoneal cavity(in the vicinity of the pancreas) and in peripancreatic tissue.Recent studies suggested that impaired clearance of injured acini by macrophages is associated with an altered cytokine reaction which may constitute a basis for progression of AP.This review focuses on the role of monocytes/macrophages in progression of AP and discusses f indings on the inflammatory process involved.

The impact of health education videos on general public’s mental health and behavior during COVID-19

Background:COVID-19 has seriously affected people’s mental health and changed their behaviors.Previous studies for mental state and behavior promotion only targeted limited people or were not suitable for daily activity restrictions.Therefore,we decided to explore the effect of health education videos on people’s mental state and health-related behaviors.Methods:Based on WeChat,QQ,and other social media,we conducted an online survey by snowball sampling.Spearman’s non-parametric method was used to analyze the correlation related to mental health problems and health-related behaviors.Besides,we used binary logistic regression analyses to examine mental health problems and health-related behaviors’predictors.We performed SPSS macro PROCESS(model 4 and model 6)to analyze mediation relationships between exposure to health education videos and depression/anxiety/health-related behaviors.These models were regarded as exploratory.Results:Binary logistic regression analyses indicated that people who watched the health education videos were more likely to wear masks(OR 1.15,p<0.001),disinfect(OR 1.26,p<0.001),and take temperature(OR 1.37,p<0.001).With higher level of posttraumatic growth(PTG)or perceived social support(PSS),people had lower percentage of depression(For PSS,OR 0.98,p<0.001;For PTG,OR 0.98,p<0.01)and anxiety(For PSS,OR 0.98,p<0.001;For PTG,OR 0.98,p=0.01)and better health behaviors.The serial multiple-mediation model supported the positive indirect effects of exposure to health education videos on the depression and three health-related behaviors through PSS and PTG(Depression:B[SE]=−0.0046[0.0021],95%CI−0.0098,−0.0012;Mask-wearing:B[SE]=0.0051[0.0023],95%CI 0.0015,0.0010;Disinfection:B[SE]=0.0059[0.0024],95%CI 0.0024,0.0012;Temperature-taking:B[SE]=0.0067[0.0026],95%CI 0.0023,0.0013).Conclusion:Exposure to health education videos can improve people’s self-perceived social support and inner growth and help them cope with the adverse impact of public health emergencies with better mental health and health-related behaviors.

Hydrogen sutfide protects colon cancer cells from chemopreventative agent β-phenylethyl isothiocvanate induced apoptosis

AIM:Hydrogen sulfide (H2S) is a prominent gaseous constituent of the gastrointestinal (GI) tract with known cytotoxic properties. Endogenous concentrations of H2S are reported to range between 0.2-3.4 mmol/L in the GI tract of mice and humans. Considering such high levels we speculate that, at non-toxic concentrations, H2S may interact with chemical agents and alter the response of colonic epithelium cells to such compounds. The GI tract is a major site for the absorption of phytochemical constituents such as isothiocyanates, flavonoids, and carotenoids, with each group having a role in the prevention of human diseases such as colon cancer. The chemopreventative properties of the phytochemical agent p-phenyethyl isothiocyanate (PEITC) are well recognized. However, little is currently known about the physiological or biochemical factors present in the GI tract that may influence the biological properties of ITCs. The current study was undertaken to determine the effects of H2S on PEITC mediated apoptosis in colon cancer cells. METHODS: Induction of apoptosis by PEITC in human colon cancer HCT116 cells was assessed using classic apoptotic markers namely SubGl population analysis, caspase-3 like activity and nuclear fragmentation and condensation coupled with the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrasodium bromide) viability assay and LDH leakage. RESULTS: PEITC significantly induced apoptosis in HCT116 cells as assessed by SubGl population formation, nuclear condensation, LDH leakage and caspase-3 activity after 24 h, these data being significant from control groups (P<0.01). In contrast, co-treatment of cells with physiological concentrations of H2S (0.1-1 mmol/L) prevented PEITC mediated apoptosis as assessed using the parameters described. CONCLUSION: PEITC effectively induced cell death in the human adenocarcinoma cell line HCT116 in vitro through classic apoptotic mechanisms. However, in the presence of H2S, apoptosis was abolished. These data suggest that H2S may play a significant role in the response of colonic epithelial cells to beneficial as well as toxic agents present within the GI tract.

Safety evaluation of nanodiamond-doxorubicin complexes in a Naïve Beagle canine model using hematologic,histological,and urine analysis

While doxorubicin(DOX)is one of the most common chemotherapeutic drugs for treating cancer,use of DOX must be managed carefully due to dose-related toxicity.Nanodiamond(ND)drug delivery system conjugated with DOX(NDX)has been reported to enhance treatment efficacy and attenuate toxicity in murine cancer models.In addition,extensive biocompatibility studies indicate that NDs seem to be well tolerated in non-human primates.Before the clinical translation of NDX,it is necessary to verify the safety of ND in large mammals.Studies of nanomedicine drug safety for large animal are not commonly reported,and this work represents a key milestone in bridging earlier advances towards clinical assessment.Herein,NDs’safety as a drug-delivery platform was evaluated in Naïve Beagle dogs.The study is performed with DOX,ND,and NDX in a dual-gender animal model using intravenous(IV)injection and hepatic portal vein(HPV)injection methods.The dogs are monitored for their health phenotype changes in continuous 5 days.Blood and urine obtained are for clinical pathology research.The results indicate that ND drug delivery platform significantly relieves DOX toxicity for Naïve Beagle dog model.This study provides guidance for the pre-clinical safety assessment of NDX therapy at large animal level.

Targeting oncogenic transcription factors for cancer therapy

Signal transducers and activators of transcription(STATs) comprise an important class of transcription factors that have been implicated in a wide variety of essential cellular functions related to proliferation,survival,and angiogenesis.Among various STAT members,STAT3 is frequently overexpressed in tumor cells as well as tissue samples,and regulates the expression of numerous oncogenic genes controlling the growth and metastasis of tumor cells.I will briefly discuss the importance of STAT3 as a potential target for prostate cancer therapy and also provide novel insights into various classes of existing pharmacological inhibitors of this transcription factor that can be potentially developed as anti-cancer drugs.

Prevalence and Prescription of Antidepressants in Depression with Somatic Comorbidity in Asia： The Research on East Asian Psychotropic Prescription Patterns Study

Background： Depression is often comorbid with chronic somatic diseases. Few previous studies have investigated the prevalence of somatic diseases in depression or the prescription pattern of antidepressants in comorbidly depressed patients in Asia. This study aimed to investigate the prevalence of somatic comorbidity （SC） in depression and compared the prescriptions of antidepressants in depressed patients with and without SC. Methods： A total of 2320 patients treated with antidepressants in 8 Asian countries were examined, and a diagnosis was based on the International Classification of Disease, 10^th revision. We listed 17 common chronic somatic diseases. Patients＇ socio-demographic and clinical characteristics and psychotropic drug prescriptions were recorded using a standardized protocol and data collection procedure. Results： Of the patients examined, 1240 were diagnosed with depression and 30% of them （n = 375） had SC. The most common comorbid condition was diabetes （23.7%）. The patients with SC were more likely to seek help at a general hospital （74.7% vs. 47.2%）, and had a higher incidence of symptoms involving sadness, disturbed sleep, and poor appetite. Noradrenergic and specific serotonergic antidepressant was prescribed more for patients with SC than for those without SC （30.4% vs, 22.9%）. Conclusions： SC is common in depressed Asian patients. It is important to strengthen the recognition of depression, especially in general hospitals and when patients report some somatic discomfort. It is also a matter of urgency to establish evidence-based guidelines for the use of new antidepressants in depressed patients with SC.

Cystathionine-γ-lyase ameliorates the histone demethylase JMJD3-mediated autoimmune response in rheumatoid arthritis

Cystathionine-γ-lyase(CSE),an enzyme associated with hydrogen sulfide(H2S)production,is an important endogenous regulator of inflammation.Jumonji domain-containing protein 3(JMJD3)is implicated in the immune response and inflammation.Here,we investigated the potential contribution of JMJD3 to endogenous CSE-mediated inflammation in rheumatoid arthritis(RA).Upregulated CSE and JMJD3 were identified in synovial fibroblasts(SFs)from RA patients as well as in the joints of arthritic mice.Knocking down CSE augmented inflammation in IL-1β-induced SFs by increasing JMJD3 expression.In addition,CSE−/−mice with collagen-induced arthritis(CIA)developed severe joint inflammation and bone erosion.Conversely,overexpressing CSE inhibited JMJD3 expression by the transcription factor Sp-1 and was accompanied by reduced inflammation in IL-1β-treated SFs.Furthermore,JMJD3 silencing or the administration of the JMJD3 inhibitor GSK-J4 significantly decreased the inflammatory response in IL-1β-treated SFs,mainly by controlling the methylation status of H3K27me3 at the promoter of its target genes.GSK-J4 markedly attenuated the severity of arthritis in CIA mice.In conclusion,suppressing JMJD3 expression by the transcription factor Sp-1 is likely responsible for the ability of CSE to negatively modulate the inflammatory response and reduce the progression of RA.

血管性认知损害诊断的进一步规范化：血管性认知损害分类共识研究组指南

引言血管性认知损害（vascular cognitive impairment,VCI）诊断共识的缺乏（体现为多种不同评估方案的使用）,妨碍了对其理解和治疗的推进.多个国家的大量临床医生和研究人员参与了2个阶段血管性认知损害分类共识研究（Vascular Impairment of Cognition Classification Consensus Study,VICCCS）,旨在就VCI的诊断原则（VICCCS-1）和诊断方案（VICCCS-2）达成一致意见.本文提供了VICCCS-2的相关内容.方法使用VICCCS-1达成的原则和已发表的诊断指南作为在线德尔菲（Delphi）调查的参考基点,以期对VCI的临床诊断达成共识.结果共进行了6轮调查,每轮有65～79名专家参与,他们就VICCCS修订的轻度和重度VCI的诊断指南达成共识,并肯定了美国国立神经疾病与卒中研究所-加拿大卒中网（National Institute of Neurological Disorders and Stroke–Canadian Stroke Network,NINDS-CSN）发布的神经心理学评估方案和对影像学检查的推荐意见.讨论VICCCS-2建议规范化应用NINDS-CSN推荐的神经心理学和影像学评估方案诊断VCI,以促进研究协作.