CHMP3 promotes the progression of hepatocellular carcinoma by inhibiting caspase­1­dependent pyroptosis.

Charged multivesicular body protein 3 (CHMP3) is an elemental constituent of the endosomal sorting complex required for transport (ESCRT) III, whose function as a tumor susceptibility gene in the development of liver cancer remains unclear. CHMP3 was found to be associated with pyroptosis by bioinformatics analysis of data from patients with hepatocellular carcinoma (HCC) in The Cancer Genome Atlas database. It was aimed to explore the role and potential mechanisms of CHMP3 in the development of liver cancer. The expression of CHMP3 at the tissue level was examined using immunohistochemistry and western blot analysis. Subsequently, HepG2 and Huh­7 cells were transfected with small interfering RNA and overexpression plasmids to change CHMP3 expression. The proliferative capacity of cells was examined using colony formation and Cell Counting Kit­8 assays. Wound healing and Transwell assays were used to examine the migratory and invasive abilities of the cells. Transmission electron microscopy was used to observe changes in cell morphology. Western blotting was used to examine the expression of caspase­1 signaling pathway related proteins, a classic pathway of pyroptosis. In addition, a xenograft tumor model was used to examine the tumorigenic ability of CHMP3 in vivo. The results demonstrated that CHMP3 expression was upregulated in HCC and was associated with poor prognosis. Knockdown or overexpression of CHMP3 inhibited or promoted the proliferation, migration and invasion of liver cancer cells. Knockdown of Huh­7 showed changes in cell membrane integrity as well as cytoplasmic leakage. Furthermore, knockdown of CHMP3 may activate the caspase­1 pyroptosis signaling pathway which in turn inhibits the progression of liver cancer, and this effect can be reversed by the caspase­1 inhibitor AYC. In conclusion, CHMP3 may affect the development of liver cancer through the caspase­1­mediated pyroptosis pathway.

Causal association between serum total bilirubin and cholelithiasis: a bidirectional two-sample Mendelian randomization study.

Background: Observational studies about the association between serum total bilirubin and cholelithiasis are inconsistent. Hence, it is essential to reevaluate the association between serum total bilirubin and cholelithiasis and to verify whether such association is causal or not. Methods: We selected single-nucleotide polymorphisms (SNPs) that are strongly associated with exposure as instrumental variable and conducted a bidirectional two-sample Mendelian randomization (MR) study to explore the causal association between serum total bilirubin and cholelithiasis. We implemented the inverse-variance weighted approach as a primary analysis to combine the Wald ratio estimates. Four additional analyses, namely, MR-Egger regression, weighted median, weighted mode, and MR-pleiotropy residual sum and outlier (PRESSO), were utilized to investigate the causal association and the influence of potential pleiotropy. Results: A total of 116 SNPs were selected as valid instrumental variables to estimate the causal association of serum total bilirubin on cholelithiasis, and causal association between genetically determined serum total bilirubin and cholelithiasis was demonstrated [beta = 0.10; 95% confident interval (CI), 0.07 to 0.14; p < 0.001]. Likewise, the other methods, namely, the weighted median (beta = 0.12; 95% CI, 0.08 to 0.15; p < 0.001), MR-Egger (beta = 0.11; 95% CI, 0.08 to 0.15; p < 0.001), weighted mode (beta = 0.11; 95% CI, 0.08 to 0.15; p < 0.001), and MR-PRESSO approaches, further confirmed that this result (p = 0.054) indicates similar results. In addition, seven SNPs were selected as instrumental variable to estimate causal association of cholelithiasis on serum total bilirubin, and the result supported the causal effect of cholelithiasis to serum total bilirubin (beta = 0.12; 95% CI, 0.09 to 0.15; p < 0.001). At the same time, the other methods, namely, the weighted median (beta = 0.10; 95% CI, 0.06 to 0.13; p < 0.001), MR-Egger (beta = 0.12; 95% CI, 0.07 to 0.18; p = 0.007), weighted mode (beta = 0.09; 95% CI, 0.03 to 0.14, p = 0.019), and MR-PRESSO methods, further confirmed this result (p < 0.001). Conclusion: Our MR study revealed that the serum total bilirubin was causally associated with the risk of cholelithiasis, and the genetic predisposition to cholelithiasis was causally associated with the increased serum total bilirubin levels.

Effectiveness and safety of central pancreatectomy in benign or low-grade malignant pancreatic body lesions: a systematic review and meta-analysis.

BACKGROUND: The best approach for treating benign or low-grade malignant lesions localized in the pancreatic neck or body remains debatable. Conventional pancreatoduodenectomy and distal pancreatectomy (DP) are associated with a risk of impairment of pancreatic function at long-term follow-up. With advances in technology and surgical skills, the use of central pancreatectomy (CP) has gradually increased. OBJECTIVES: The objective was to compare the safety, feasibility, and short-term and long-term clinical benefits of CP and DP in matched cases. METHODS: The PubMed, MEDLINE, Web of Science, Cochrane, and EMBASE databases were systematically searched to identify studies published from database inception to February 2022 that compared CP and DP. This meta-analysis was performed using R software. RESULTS: Twenty-six studies matched the selection criteria, including 774 CP and 1713 DP cases. CP was significantly associated with longer operative time ( P <0.0001), less blood loss ( P <0.01), overall and clinically relevant pancreatic fistula ( P <0.0001), postoperative hemorrhage ( P <0.0001), reoperation ( P =0.0196), delayed gastric emptying ( P =0.0096), increased hospital stay ( P =0.0002), intra-abdominal abscess or effusion ( P =0.0161), higher morbidity ( P <0.0001) and severe morbidity ( P <0.0001) but with a significantly lower incidence of overall endocrine and exocrine insufficiency ( P <0.01), and new-onset and worsening diabetes mellitus ( P <0.0001) than DP. CONCLUSIONS: CP should be considered as an alternative to DP in selected cases such as without pancreatic disease, length of the residual distal pancreas is more than 5 cm, branch-duct intraductal papillary mucinous neoplasms, and a low risk of postoperative pancreatic fistula after adequate evaluation.

Laparoscopic surgery for gallstones or common bile duct stones: A stably safe and feasible surgical strategy for patients with a history of upper abdominal surgery.

Backgrounds/Aims: A history of upper abdominal surgery has been identified as a relative contraindication for laparoscopy. This study aimed to compare the clinical efficacy and safety of laparoscopic cholecystectomy (LC) and laparoscopic common bile duct exploration (LCBDE) in patients with and without previous upper abdominal surgery. Methods: In total, 131 patients with previous upper abdominal surgery and 64 without upper abdominal surgery underwent LC or LCBDE between September 2017 and September 2021 at the Shengjing Hospital of China Medical University. Patients with previous upper abdominal surgery were divided into four groups: group A included patients with previous right upper abdominal surgery who underwent LC (n = 17), group B included patients with previous other upper abdominal surgery who underwent LC (n = 66), group C included patients with previous right upper abdominal surgery who underwent LCBDE (n = 30), and group D included patients with previous other upper abdominal surgery who underwent LCBDE (n = 18). Patient demographics and perioperative outcomes were retrospectively analyzed. Results: The preoperative liver function indexes showed no significant difference between the observation and control groups. For patients who underwent LC, groups A and B had more abdominal adhesions than the control group. One case was converted to open surgery in each of groups A and B. There was no statistical difference in operation time, estimated blood loss, postoperative hospital stay, and drainage volume. For patients who underwent LCBDE, groups C and D had more estimated blood loss than the control group (group C, 41.33 ± 50.84 vs. 18.97 ± 13.12 ml, p = 0.026; group D, 66.11 ± 87.46 vs. 18.97 ± 13.12 ml, p = 0.036). Compared with the control group, group C exhibited longer operative time (173.87 ± 60.91 vs. 138.38 ± 57.38 min, p = 0.025), higher drainage volume (296.83 ± 282.97 vs. 150.83 ± 127.04 ml, p = 0.015), and longer postoperative hospital stay (7.97 ± 3.68 vs. 6.17 ± 1.63 days, p = 0.021). There was no mortality in all groups. Conclusions: LC or LCBDE is a safe and feasible procedure for experienced laparoscopic surgeons to perform on patients with previous upper abdominal surgery.

Association between tea intake and hospitalized nephrolithiasis in Chinese adults: A case-control study.

Introduction and aim: Nephrolithiasis is one of the most common urological disorders worldwide. Tea is one of the most popular drinks worldwide. This study aimed to explore the association between tea intake and hospitalized nephrolithiasis in Chinese adults. Methods: The patients and healthy participants were from the Shenyang sub-cohort of Tianjin Chronic Low-Grade Systemic Inflammation and Health Cohort Study. After selecting and matching by age (±1 year) and sex using the 1:2 ratio, 834 participants were included in this study. Of these, 278 patients had hospitalized nephrolithiasis and 556 were healthy controls. The tea intake was assessed using a validated self-administered food frequency questionnaire. Multivariate conditional logistic regression analysis was used to evaluate the association between tea intake and hospitalized nephrolithiasis. Results: After adjustment, a higher frequency of tea intake was found to be negatively associated with the risk of hospitalized nephrolithiasis. Compared with participants who never drank tea, the odds ratio (95% confidence interval) [OR (95% CI)] for participants who drank ≥1 cup (180 mL) of tea per day was 0.418 (0.192-0.911) (P for trend = 0.013). Moreover, the adjusted OR (95% CI) for participants who drank ≥1 cup of green tea and black tea per day was 0.189 (0.069-0.520) (P for trend <0.001) and 1.248 (0.437-3.559) (P for trend = 0.654), respectively. Conclusions: Increased tea intake was found to be associated with a lower risk of hospitalized nephrolithiasis among Chinese adults. This finding may assist in the prevention of hospitalized nephrolithiasis.

Developments in the Diagnosis and Management of Cholecystoenteric Fistula.

Background: Cholecystoenteric fistula (CEF) is a rare complication of cholelithiasis. CEF refers to one or more pathological perforations between the gallbladder and the adjacent gastrointestinal tract, first described by Bartholin in 1645. The aim of this review is to examine the etiology, symptoms, diagnosis, and treatment of CEF.Methods: A literature search was conducted according to a set of criteria in PubMed for historical and current peer-reviewed studies regarding CEF.Results: Clinical manifestations of CEF are always latent. Despite modern imaging studies and diagnostic methods, it is still very difficult to definitively diagnose CEF preoperatively. Instead, CEF is often accidentally discovered in the perioperative period or via intraoperative exploration.Conclusions: Without appropriate preoperative preparation, gastrointestinal injury and intraoperative bleeding often occur. CEF often goes unreported, and its diagnosis and treatment are still controversial. Early diagnosis of CEF is essential for effective treatment and improved outcome.

Osthole: An up-to-date review of its anticancer potential and mechanisms of action.

With its high incidence and mortality rates, cancer is one of the largest health problems worldwide. Investigating various cancer treatment options has been the focus of many domestic and international researchers, and significant progress has been made in the study of the anticancer effects of traditional Chinese medicines. Osthole, a coumarin compound extracted from Cnidium monnieri (L.) Cuss., has become a new research hotspot. There have been many reports on its anticancer effects, and recent studies have elucidated that its underlying mechanism of action mainly involves inhibiting cancer cell proliferation, inducing cancer cell apoptosis, inhibiting invasion and migration of cancer cells, inhibiting cancer angiogenesis, increasing sensitivity to chemotherapy drugs, and reversing multidrug resistance of cancer cells. This mini-review summarizes the research progress on the anticancer effects of osthole in recent years.

Role of Forkhead Box O Proteins in Hepatocellular Carcinoma Biology and Progression (Review).

Hepatocellular carcinoma (HCC), the most common type of malignant tumor of the digestive system, is associated with high morbidity and mortality. The main treatment for HCC is surgical resection. Advanced disease, recurrence, and metastasis are the main factors affecting prognosis. Chemotherapy and radiotherapy are not sufficiently efficacious for the treatment of primary and metastatic HCC; therefore, optimizing targeted therapy is essential for improving outcomes. Forkhead box O (FOXO) proteins are widely expressed in cells and function to integrate a variety of growth factors, oxidative stress signals, and other stimulatory signals, thereby inducing the specific expression of downstream signal factors and regulation of the cell cycle, senescence, apoptosis, oxidative stress, HCC development, and chemotherapy sensitivity. Accordingly, FOXO proteins are considered multifunctional targets of cancer treatment. The current review discusses the roles of FOXO proteins, particularly FOXO1, FOXO3, FOXO4, and FOXO6, in HCC and establishes a theoretical basis for the potential targeted therapy of HCC.

Tetramethylpyrazine: A Review of Its Antitumor Potential and Mechanisms.

Cancer remains a major public health threat. The mitigation of the associated morbidity and mortality remains a major research focus. From a molecular biological perspective, cancer is defined as uncontrolled cell division and abnormal cell growth caused by various gene mutations. Therefore, there remains an urgent need to develop safe and effective antitumor drugs. The antitumor effect of plant extracts, which are characterized by relatively low toxicity and adverse effect, has attracted significant attention. For example, increasing attention has been paid to the antitumor effects of tetramethylpyrazine (TMP), the active component of the Chinese medicine Chuanqiong, which can affect tumor cell proliferation, apoptosis, invasion, metastasis, and angiogenesis, as well as reverse chemotherapeutic resistance in neoplasms, thereby triggering antitumor effects. Moreover, TMP can be used in combination with chemotherapeutic agents to enhance their effects and reduce the side effect associated with chemotherapy. Herein, we review the antitumor effects of TMP to provide a theoretical basis and foundation for the further exploration of its underlying antitumor mechanisms and promoting its clinical application.

Characterization and chemical modification of PLN-1, an exopolysaccharide from Phomopsis liquidambari NJUSTb1.

Phomopsis liquidambari is a classical endophytic fungus with great application potential in ecology and agriculture; however, studies on its exopolysaccharides are lacking. Here, we aimed to evaluate the structure and bioactivity of PLN-1, an exopolysaccharide derived from the P. liquidambari NJUSTb1 strain. The structure was elucidated by chromatography/spectral methods and hydrolyzation. Immunomodulation, moisture absorption, and retention properties were investigated after sulfation and carboxymethylation modification. Results showed that PLN-1 contained a linear repeating unit of →[4)-α-d-Glcp-(1→6)-α-d-Glcp-(1→4)-α-d-Glcp-(1→4)-α-d-Glcp-(1→]n, with a molecular weight of 343 kDa. The degrees of substitution of sulfated polysaccharide (S-PLN-1) and carboxymethylated polysaccharide (C-PLN-1) were 1.228 and 0.903, respectively. S-PLN-1 showed stronger moisture absorption and retention properties than PLN (crude EPS), C-PLN1, and PLN-1. Furthermore, PLN, S-PLN-1, and C-PLN-1 stimulated the proliferation of RAW 264.7 cells with no cytotoxicity. The elucidation of PLN-1 in this study paves the way for future applications.

Anti-Biofilm and Antivirulence Activities of Metabolites from Plectosphaerella cucumerina against Pseudomonas aeruginosa.

This study reported the efficacy of the metabolites of Plectosphaerella cucumerina, one phyllosphere fungus from Orychophragmus violaceus, against Pseudomonas aeruginosa quorum sensing (QS) and QS-regulated biofilms. The minimum inhibitory concentration (MIC) of the ethyl acetate (EtOAc) extract from P. cucumerina against P. aeruginosa PAO1 was 1.25 mg mL-1. At sub-MIC concentrations, P. cucumerina extract (0.25-1 mg mL-1) not only inhibited biofilm formation but also disrupted preformed biofilms of P. aeruginosa PAO1 without affecting its growth. Fluorescence and scanning electron microscope (SEM) showed architectural disruption of the biofilms when treated with P. cucumerina metabolites. Further investigation demonstrated that metabolites in P. cucumerina attenuated the QS-dependent virulence factors. LC-MS/MS spectra coupled with experimentally standard samples suggested that patulin and emodin might act as the principal components possessing anti-biofilm and antivirulence activities. This is the first report of (1) the isolation of P. cucumerina from the phyllosphere of O. violaceus and (2) anti-biofilm, antivirulence, and biofilm disruption activities of this fungus. Thus, this study provides fascinating new pathways for screening antipathogenic agents.