Success rate of current human-derived gastric cancer organoids establishment and influencing factors: A systematic review and meta-analysis.

BACKGROUND: Human-derived gastric cancer organoids (GCOs) are widely used in gastric cancer research; however, the culture success rate is generally low. AIM: To explore the potential influencing factors, and the literature on successful culture rates of GCOs was reviewed using meta-analysis. METHODS: PubMed, Web of Science, and EMBASE were searched for studies. Two trained researchers selected the studies and extracted data. STATA 17.0 software was used for meta-analysis of the incidence of each outcome event. The adjusted Methodological Index for Non-Randomized Studies scale was used to assess the quality of the included studies. Funnel plots and Egger's test were used to detect publication bias. Subgroup analyses were conducted for sex, tissue source, histological classification, and the pathological tumor-node-metastasis (pTNM) cancer staging system. RESULTS: Eight studies with a pooled success rate of 66.6% were included. GCOs derived from women and men had success rates of 67% and 46.7%, respectively. GCOs from surgery or biopsy/endoscopic submucosal dissection showed success rates of 70.9% and 53.7%, respectively. GCOs of poorly-differentiated, moderately-differentiated and signet-ring cell cancer showed success rates of 64.6%, 31%, and 32.7%, respectively. GCOs with pTNM stages I-II and III-IV showed success rates of 38.3% and 65.2%, respectively. Y-27632 and non-Y-27632 use showed success rates of 58.2% and 70%, respectively. GCOs generated with collagenase were more successful than those constructed with Liberase TH and TrypLE (72.1% vs 71%, respectively). EDTA digestion showed a 50% lower success rate than other methods (P = 0.04). CONCLUSION: GCO establishment rate is low and varies by sex, tissue source, histological type, and pTNM stage. Omitting Y-27632, and using Liberase TH, TrypLE, or collagenase yields greater success than EDTA.

Bibliometrics analysis based on the Web of Science: Current trends and perspective of gastric organoid during 2010-2023.

BACKGROUND: Three-dimensional organoid culture systems have been established as a robust tool for elucidating mechanisms and performing drug efficacy testing. The use of gastric organoid models holds significant promise for advancing personalized medicine research. However, a comprehensive bibliometric review of this bur-geoning field has not yet been published. AIM: To analyze and understand the development, impact, and direction of gastric organoid research using bibliometric methods using data from the Web of Science Core Collection (WoSCC) database. METHODS: This analysis encompassed literature pertaining to gastric organoids published between 2010 and 2023, as indexed in the WoSCC. CiteSpace and VOSviewer were used to depict network maps illustrating collaborations among authors, institutions and keywords related to gastric organoid. Citation, co-citation, and burst analysis methodologies were applied to assess the impact and progress of research. RESULTS: A total of 656 relevant studies were evaluated. The majority of research was published in gastroenterology-focused journals. Globally, Yana Zavros, Hans Clevers, James M Wells, Sina Bartfeld, and Chen Zheng were the 5 most productive authors, while Hans Clevers, Huch Meritxell, Johan H van Es, Marc Van de Wetering, and Sato Toshiro were the foremost influential scientists in this area. Institutions from the University Medical Center Utrecht, Netherlands Institute for Developmental Biology (Utrecht), and University of Cincinnati (Cincinnati, OH, United States) made the most significant contributions. Currently, gastric organoids are used mainly in studies investigating gastric cancer (GC), Helicobacter pylori-infective gastritis, with a focus on the mechanisms of GC, and drug screening tests. CONCLUSION: Key focus areas of research using gastric organoids include unraveling disease mechanisms and enhancing drug screening techniques. Major contributions from renowned academic institutions highlight this field's dynamic growth.

Clinical experience in laparoscopic treatment of gallbladder perforation.

Aim: We herein present our clinical experience in laparoscopic surgery for gallbladder perforation (GBP). Materials and Methods: Retrospective analysis was performed on the clinical data of 44 patients who diagnosed with GBP from January 2015 to November 2020. Results: The mean age of the 44 patients was 64.0 years and the female-to-male ratio was 20:24. The most common type of GBP was Type II, followed by Type I and Type III (31:9:4). 72.7% of the patients were diagnosed with GBP at the time of surgery. Laparoscopic surgery was performed for 38 (86.4%) patients, with a conversion rate of 13.2%. The mean length of hospital stays was 7.8 days. The mortality and morbidity rates were 2.3% and 11.4%, respectively. Conclusions: Pre-operative diagnosis of GBP is difficult. Laparoscopic surgery is safe, feasible and effective for patients with GBP.

Radical Annulation of 2-Cyanoaryl Acrylamides via C═C Double Bond Cleavage: Access to Amino-Substituted 2-Quinolones.

A novel annulation of 2-cyanoaryl acrylamides via C═C double bond cleavage has been developed for facile and efficient access to a broad spectrum of functionalized 4-amino-2-quinolones, which are important N-heterocycles. In this transformation, the solvent THF is demonstrated to play a crucial role, and the addition of alkyl radicals to nitrile, 1,5-hydride shift, and cleavage of the C-C bond are involved in the mechanism.

Decarboxylative Oxyacyloxylation of Propiolic Acids: Construction of Alkynyl-Containing α-Acyloxy Ketones.

Novel decarboxylative oxyacyloxylation of propiolic acids has been developed. This reaction provides an efficient access to alkynyl-containing α-acyloxy ketones from readily available starting materials and exhibits significant functional group tolerance. Furthermore, oxyacyloxylation of terminal alkynes and aliphatic propiolic acids was also developed. A possible reaction mechanism is proposed based on mechanistic studies.

Copper-Catalyzed Decarboxylative Cycloaddition of Propiolic Acids, Azides, and Arylboronic Acids: Construction of Fully Substituted 1,2,3-Triazoles.

A copper-catalyzed decarboxylative cycloaddition of propiolic acids, azides, and arylboronic acids is described. The present reaction provides an efficient and convenient method for the synthesis of various fully substituted 1,2,3-triazoles from readily available starting materials. A possible mechanism is proposed.

HSP90 as a novel therapeutic target for posterior capsule opacification.

Posterior capsule opacification (PCO) is a common complication of cataract surgery, resulting from a combination of proliferation, migration, epithelial-mesenchymal transition (EMT) of residual capsular epithelial cells and fibrosis of myofibroblasts. HSP90 is known to regulate the proteostasis of cells under pathophysiological conditions. The role of HSP90 in PCO formation, however, is not clear. To do this, the lens epithelial cell lines and an ex vivo cultured rat capsular bag model were used to study the role of HSP90 in PCO formation. The expression of protein and mRNA was measured by immunoblotting and quantitative RT-PCR, and cell apoptosis was measured by TUNEL(TdT-mediated dUTP nick-end labeling). The cell proliferation was measured by cell viability assays. The results showed that 17-AAG (Tanespimycin), an inhibitor of HSP90, suppresses the proliferation of immortalized lens epithelial cell lines HLE-B3, SRA01/04, and mLEC, with IC50 values of 0.27, 0.27, and 0.49 µM, respectively. In an ex vivo cultured rat capsular model, the capsular residual epithelial cells resisted the stress of the capsulorhexis surgery and took 3-6 days to completely overlay the capsular posterior wall. During this process, heat shock factor 1 and its downstream targets HSP90, HSP25, αB-crystallin, and HSP40 were upregulated. Treatment with 17-AAG inhibited the viability of capsular residual epithelial cells and induced the cells apoptosis, characterized by increases in ROS levels, apoptotic DNA injury, and the activation of caspases 9 and 3. HSP90 participated in regulating both EGF receptor (EGFR) and TGF receptor (TGFR) signaling pathways. HSP90 was found to interact with the EGFR, such that inhibition of HSP90 by 17-AAG destabilized the EGFR protein and suppressed p-ERK1/2 and p-AKT levels. 17-AAG also inhibited the TGF-ß-induced phosphorylation of SMAD2/3 and ERK1/2 and the decrease in E-cadherin and ZO-1 expression. Accordingly, these data suggest that the induction of HSP90 protects capsular residual epithelial cells against capsulorhexis-induced stress and participates in regulating the processes of proliferation, EMT and migration of rat capsular residual epithelial cells, at least partly, through the EGFR and TGFR signaling pathways. Treatment with 17-AAG suppresses PCO formation and is therefore a potential therapeutic candidate for PCO prevention.

Decarboxylative cascade cyclization of α-keto acids with 2-cyano-3-arylaniline-derived acrylamides.

An oxidative decarboxylative cascade cyclization of α-keto acids with 2-cyano-3-arylaniline-derived acrylamides was developed. This cascade reaction exhibits a broad substrate scope, and provides an efficient access to carbonyl-containing pyrido[4,3,2-gh]phenanthridines. A possible mechanism is proposed.

Copper-Catalyzed Decarboxylative Oxyalkylation of Alkynyl Carboxylic Acids: Synthesis of γ-Diketones and γ-Ketonitriles.

A novel copper-catalyzed decarboxylative oxyalkylation of alkynyl carboxylic acids with ketones and alkylnitriles via direct C(sp3)-H bond functionalization to construct new C-C bonds and C-O double bonds was developed. This transformation is featured by wide functional group compatibility and the use of readily available reagents, thus affording a general approach to γ-diketones and γ-ketonitriles. A possible mechanism is proposed.

Recent advances in understanding of amino acid signaling to mTORC1 activation.

The mechanistic target of rapamycin complex 1 (mTORC1) is a master controller of cell growth and metabolism which integrates diverse bio-signaling inputs to coordinate various fundamental biological processes. Amino acids, especially leucine, arginine and glutamine, signal to mTORC1 activation. Classically, Rag GTPases play a crucial role in amino acids-induced mTORC1 activation in the lysosome and Golgi apparatus. More recently, multiple amino acid sensors have been identified and most of them indirectly associate with Rag GTPases. As a result, the mechanistic details on how amino acids are sensed and activate mTORC1 are rapidly evolving. This review discusses current understanding of mTORC1 activation and provides a brief and up-to-date narrative on the progress of amino acid sensors regulating mTORC1 activation.

Metal-Free Radical [2 + 2 + 1] Cyclization of ortho-Cyanoarylacrylamides with Alkyl Nitriles: Synthesis of Pyrrolo[3,2- c]quinolines.

A novel radical [2 + 2 + 1] cyclization of ortho-cyanoarylacrylamides with dual α-C-H bonds in alkyl nitriles has been developed. The reaction provides new facile and straightforward access to cyano-substituted pyrrolo[3,2- c]quinolines, which are important nitrogen-containing polyheterocycles. A possible mechanism for the transformation is proposed.

Downregulation of heat shock factor 4 transcription activity via MAPKinase phosphorylation at Serine 299.

Dysfunction of HSF4 is associated with congenital cataracts. HSF4 transcription activity is turned on and regulated by phosphorylation during early postnatal lens development. Our previous data suggested that mutation HSF4b/S299A can upregulate HSF4 transcription activity in vitro, but the biological significance of posttranslational modification on HSF4/S299 during lens development remains unclear. Here, we found that the mutation HSF4/S299A can upregulate the expression of HSP25 and alpha B-crystallin at both protein and mRNA levels in mouse the lens epithelial cell line, but HSF4/S299D does not. Using the rabbit polyclonal antibody against phospho-S299 of HSF4, we found that EGF and ectopic expression of MEK1 can increase the phosphorylation of HSF4/S299 and induce HSF4 sumoylation, and these effects are inhibited by U0126. ERK1/2 can phosphorylate the S299 in HSF4/wt but not in HSF4/S299A in the in vitro kinase assay. Functionally, ectopic MEK1 can inhibit HSF4-controled alpha B-crystallin expression but has less effect on HSF4/S299A. EGF can upregulate phospho-HSF4/S299 and downregulate alpha B-crystallin expression in P3 mouse lens, and this downregulation is suppressed by U0126. During mouse lens development, phosphorylation of HSF4/S299 is downregulated in P3 lens and upregulated in P7 and P14 lens. However, in 2 months old lens, both phosphorylation of HSF4/S299 and total HSF4 protein are decreased. Interestingly, ERK1/2 activity is lower in P3 lens than in P7 and P14 lens, which is in line with the phosphorylation of HSF4/S299. Taken together, our data demonstrate that HSF4/299 is a phosphorylation target of MEK1-ERK1/2, and phosphorylation of S299 is responsible for tuning down HSF4 transcription activity during postnatal lens development.

[Stroke-induced acroparalysis treated with xunjingcuiqi needling technique: a randomized controlled trial].

OBJECTIVE: To observe the impacts on the muscle strength in the patients of stroke-induced acroparalysis treated with Xunjingcuiqi needling technique. METHODS: One hundred patients were randomized into a Xunjingcuiqi group and a routine acupuncture group, 50 cases in each group. In the routine acupuncture group, the routine acupuncture technique was adopted at the main acupoints, such as Shangxing (GV 23), Baihui (GV 20), Dicang (ST 4), Quchi (LI 11), Huantiao (GB 30) and Zusanli (ST 36), etc. In Xunjingcuiqi group, on the basis of the routine acupuncture technique, Xunjingcuiqi needling technique (pricking technique was quickly applied with the filiform needle along the running course of meridian to promote the conduction of meridian qi) was added. For the patients being hard to feel the needling sensation and with the muscle strength of 0 to 1 degree, Dongzhencuiqi technique was supplemented at shu-stream points of yang meridians (after qi arrival, the needling manipulation with limb movement was given to promote the conduction of meridian qi). The treatment was given once every day in the two groups. Ten treatments made one session. Three sessions of treatment were required. At the end of each session treatment, the muscle strength and clinical efficacy were assessed. RESULTS: In the 1st, 2nd and 3rd sessions of treatment, 20, 24 and 36 cases achieved the 3 to 5 degrees muscle strength in Xunjingcuiqi group, respectively; and 6, 10 and 15 cases achieved the 3 to 5 degrees muscle strength in the routine acupuncture group. The differences were significant statistically in comparison of the two groups (P < 0.01, P < 0.05). The markably effective rates were 60.0% (30/50), 64.0% (32/50) and 70.0% (35/50) after the 1st, 2nd and 3rd sessions of treatment in Xunjingcuiqi group, respectively; and those were 38.0% (19/50), 44.0% (22/50) and 46.0% (23/50) in the routine acupuncture group, respectively. The differences were significant in the 1st and 3rd sessions of treatment between the two groups (both P < 0.05). CONCLUSION: Xunjingcuiqi needling technique combined with routine acupuncture achieves the apparent superior efficacy on acroparalysis induced by ischemic stroke as compared with the simple routine acupuncture. Xunjingcuiqi needling technique obviously improves muscle strength and shortens the duration of sickness.

Matrix metalloproteinases and their multiple roles in Alzheimer's disease.

Alzheimer's disease (AD) is the most prevalent type of dementia. Pathological changes in the AD brain include amyloid-ß (Aß) plaques and neurofibrillary tangles (NFTs), as well as neuronal death and synaptic loss. Matrix metalloproteinases (MMPs) play an important role as inflammatory components in the pathogenesis of AD. MMP-2 might be assumed to have a protective role in AD and is the major MMP which is directly linked to Aß in the brain. Synthesis of MMP-9 can be induced by Aß, and the enzymes appear to exert multiple effects in AD in senile plaque homoeostasis. The proaggregatory influence on tau oligomer formation in strategic brain regions may be a potential neurotoxic side effect of MMP-9. MMP-3 levels are correlated to the duration of AD and correlate with the CSF T-tau and P-tau levels in the elderly controls. Elevated brain levels of MMP-3 might result in increased MMP-9 activity and indirectly facilitate tau aggregation. At present, the clinical utility of these proteins, particularly in plasma or serum, as potential early diagnostic biomarkers for AD remains to be established. More research is needed to understand the diverse roles of these proteases to design specific drugs and devise therapeutic strategies for AD.

Blocking beta2-adrenergic receptor attenuates acute stress-induced amyloid beta peptides production.

Environmental factors play an important role in the Alzheimer's disease (AD) development and stress may accelerate the progression of AD. Beta-adrenergic receptors are activated by stress and may influence different aspects of cognitive function. So, it was hypothesized that stress may accelerate the pathological progression of AD by the activation of beta(2)-adrenergic receptor (beta(2)-AR). We have investigated the role of acute stress and activation of beta(2)-AR in amyloid beta (Abeta) peptides production in a mouse model of acute restraint stress. Injections of the beta(2)-AR-selective agonist clenbuterol hydrochloride enhanced the production of acute stress-induced Abeta peptides production; the beta(2)-AR-selective antagonist ICI 118,551 reduced Abeta peptides production. It is suggested that acute stress induces abnormal activation of beta(2)-AR which subsequently enhances Abeta peptides (the main neuropathological hallmarks of AD) production possibly resulting in the onset of AD. The findings indicate that new therapeutic strategies designed to blocking beta(2)-AR might be valuable for the prevention and treatment of AD.

[Effect of Liuwei Dihuang soft capsule and Ginkgo leaf tablet on serum regulated upon activation, normal T cell expressed and secreted in patients with diabetes mellitus type 2].

OBJECTIVE: To investigate the effect of Liuwei Dihuang Soft Capsule(LDSC) and Ginkgo Leaf Tablet (GLT) on serum regulated upon activation, normal T cell expressed and secreted (RANTES) in the patients with diabetes mellitus type 2 (DM2). METHODS: Forty patients with early stage DM2 were randomly assigned to two groups, 20 in each group. Based on the conventional treatment with hypoglycemic agents, patients in the treated group were treated with LDSC plus GLT additionally, and those in the placebo group with placebo for 6 months, respectively. The levels of serum RANTES, blood glucose, blood lipids and glycosylated hemoglobin, as well as micro-content of albumin in urine were measured before and after treatment. RESULTS: In the treated group, the serum level of RANTES decreased significantly after treatment, and it was significantly lower as compared with that in the control group (P < 0.05). CONCLUSIONS: LDSC and GLT can decrease serum RANTES level in patients with DM2. They play a preventive and therapeutic role on diabetic complications by their anti-inflammatory effect.

Orientated thermotherapy of ferromagnetic thermoseed in hepatic tumors.

AIM:To study the thermotherapeutic effects of implanted ferromagnetic thermoseeds in high frequency electromagnetic field in hepatic tumors.METHODS:The ferromagnetic thermoseeds made of nickel-copper alloy, which has a lower Curie temperature, were implanted into hepatic tumors of mice. The high frequency electromagnetic field was then applied in vitro to make the ferromagnetic thermoseeds produce the hyperthermia. Before and after thermotherapy, the tumor size, pathologic alteration and animal survival period were assessed.RESULTS:The temperature at the central area of the tumor could be heated up to 50°. Most of tumors in mice disappeared with a large amount of tumor necrosis. The survival period of mice was prolonged.CONCLUSION:This thermotherapy is beneficial to directional selection and temperature control for treatment of hepatic tumors.