Naringenin Induces HepG2 Cell Apoptosis via ROS-Mediated JAK-2/STAT-3 Signaling Pathways.

Hepatocarcinoma is one of the most prevalent digestive system tumors worldwide and lacks effective therapy. Recently, naringenin has been isolated from some citrus fruits, and its anticancer effects have been tested. However, the molecular mechanisms of naringenin and the potential implications of oxidative stress in naringenin-induced cytotoxicity in HepG2 cells remain elusive. Based on the above, the present study examined the effect of naringenin on the cytotoxic and anticancer mechanisms of HepG2 cells. Naringenin-induced HepG2 cell apoptosis was confirmed via the accumulation of the sub-G1 cell population, phosphatidylserine exposure, mitochondrial transmembrane potential loss, DNA fragmentation, caspase-3 activation, and caspase-9 activation. Furthermore, naringenin enhanced cytotoxic effects on HepG2 cells and triggered intracellular reactive oxygen species; the signaling pathways of JAK-2/STAT-3 were inhibited, and caspase-3 was activated to advance cell apoptosis. These results suggest that naringenin plays an important role in inducing apoptosis in HepG2 cells and that naringenin may be a promising candidate for cancer therapy.

Comparative efficiency and safety of insulin degludec/aspart with insulin glargine in type 2 diabetes: a meta-analysis of randomized controlled trials.

Recent studies have found compared with insulin glargine (IGlar), insulin degludec/aspart (IDeg/Asp) may provide adequate glycemic control and prevent hypoglycemia events in type 2 diabetes mellitus (T2DM). Consequently, we performed a meta-analysis to appraise and compare the efficiency and safety of IDeg/Asp and IGlar in the treatment of T2DM. We sought the databases including PubMed, Embase, Scopus, Cochrane library to confirm related articles which inspected the effect of IDeg/Asp versus IGlar for the treatment of T2DM until May 2021. Finally, six randomized controlled trials (RCTs) of 1,346 patients were included. The results showed that IDeg/Asp significantly decreased the mean hemoglobin A1c (HbA1c) level but was prone to serious adverse events, and IGlar increased the nocturnal confirmed hypoglycemia events. Besides, there were no significant changes in other indicators, including mean fasting plasma glucose (FPG) level, nine-point self-measured plasma glucose (SMPG) level, and adverse events. What's more, we found that there was no significant difference in the occurrence of hypoglycemia overall, but our subgroup analysis of confirmed hypoglycemia revealed the population in this subgroup (duration of diabetes ≤11 years) might has its particularity effecting the hypoglycemia outcome. Concerning efficiency, IDeg/Asp may have advantages in controlling the mean HbA1c level. Regarding safety, IGlar might increase the risk of nocturnal confirmed hypoglycemia. Further evidence is needed to compare better the efficiency and safety of IDeg/Asp versus IGlar therapy.

Silver-Promoted Decarboxylative Sulfonylation of Aromatic Carboxylic Acids with Sodium Sulfinates.

A novel and efficient synthesis of sulfones was developed via a silver-promoted decarboxylative sulfonylation reaction between aromatic carboxylic acids and sodium sulfinates for the first time. The approach features operational simplicity and good functional group compatibility and uses readily available starting materials. Furthermore, mechanistic studies reveal that the decarboxylative sulfonylation reaction is likely to proceed via a radical mechanism.

Synthesis of Benzofulvenes via Cp*Co(III)-Catalyzed C-H Activation and Carbocyclization of Aromatic Ketones with Internal Alkynes.

A highly efficient and practical synthesis of benzofulvenes was developed via ketone-directed Cp*Co(III)-catalyzed sequential C-H activation, addition, cyclization, and dehydration cascade processes between simple aromatic ketones and alkynes. The reaction tolerates a variety of functional groups, and various benzofulvenes were efficiently synthesized in 42-92% yields.

Synthesis of Aryl Alkynes via Copper Catalyzed Decarboxylative Alkynylation of 2-Nitrobenzoic Acids.

An efficient protocol for the synthesis of internal aryl alkynes was achieved via Cu-catalyzed decarboxylative cross-coupling reactions, and to the best of our knowledge, this is the first example of a Cu-catalyzed decarboxylative alkynylation of benzoic acids with terminal alkynes. This approach utilizes simple Cu salt as catalyst and O2, an abundant, clean, and green material, as the oxidant. The reaction tolerates various functional groups, and a variety of internal aryl alkynes were synthesized in 46-83% yields.

Impact of smoking cessation duration on lung cancer mortality: A systematic review and meta-analysis.

BACKGROUND: Smoking history is a heterogeneous situation for different populations, and numerous studies suggest that smoking cessation is conducive to reduce the mortality of lung cancer. However, no quantitative meta-analysis regarding smoking cessation duration based on different populations has demonstrated it clearly. METHODS: We systematically searched four electronic databases (PubMed, Embase, the Cochrane Central Register of Controlled Trials, and Scoups) till February 2023. Eligible studies reported the association between lung cancer survival and duration of smoking cessation. Additionally, we stratified the study population according to whether they had lung cancer at the time they quit smoking. Studies were pooled with the random-effects model. RESULTS: Out of the 11,361 potential studies initially identified, we included 24 studies involving 969,560 individuals in our analysis. Lung cancer mortality varied across two groups: general quitters and peri-diagnosis quitters. For general quitters, those who had quit smoking for less than 10 years exhibited an RR of 0.64 (95% CI [0.55-0.76]), while those who quit for 10-20 years had an RR of 0.33 (0.25-0.43), over 20 years had an RR of 0.16 (0.11-0.24), and never-smokers had an RR at 0.11 (0.07-0.15). Among peri-diagnosis quitters, the 1-year Overall Survival (OS) showed an RR of 0.80 (0.67-0.96), the 2-year OS had an RR of 0.89 (0.80-0.98), the 3-year OS had an RR of 0.93 (0.84-1.03), and the 5-year OS had an RR of 0.85 (0.76-0.96). CONCLUSIONS: Earlier and longer smoking cessation is associated with reduced lung cancer mortality, no matter in which cessation stage for two different populations.

Mutagenesis selection and large-scale cultivation of non-green Chlamydomonas reinhardtii for food applications.

Background: The green alga Chlamydomonas reinhardtii is an accepted food ingredient in the United States of America (United States), the European Union, Singapore, and China. It can be consumed in unlimited quantities. As this alga is rich in nutrients, proteins, and rough polysaccharides and contains a balanced proportion of various amino acids, it is an excellent raw material for food production. Although various edible brown and green algae are available on the market, their color and strong grassy flavor have constrained their popularity among consumers, thereby limiting their application in food additives and animal feed. Methods: Chlorophyll-deficient C. reinhardtii mutants were developed using atmospheric and room temperature plasma (ARTP) technology. Results: A yellow-colored C. reinhardtii variant (A7S80) cultivated in dark conditions was isolated. This light-sensitive variant has a mutation in the chlM gene, and it can grow heterotrophically using acetate as a carbon source. Conclusion: Compared to wild-type C. reinhardtii, A7S80 has significantly lower chlorophyll levels, reduced grassy flavor, and more diverse pigments, with considerable potential for commercial application in human and animal food production, as well as in pharmaceutical and cosmetic industries.

Efficacy and relative safety of caplacizumab in immune-mediated thrombotic thrombocytopenic purpura: a systematic review and meta-analysis.

Immune-mediated thrombotic thrombocytopenia purpura (iTTP) is a rare microvascular disease characterized by severe disseminated microvascular thrombose-bleeding syndrome. Caplacizumab has been approved for the treatment of iTTP in combination with Plasma Exchange (PE) and immunosuppressive therapy, but its role in iTTP therapy remains uncertain. Therefore, we conducted a meta-analysis to investigate the safety and efficacy of caplacizumab for the treatment of patients with iTTP. We searched electronic databases (PubMed, Embase, Cochrane Library, and Scopus) and reference lists of relevant articles to find articles published from 2015 to 2022. The time to normalization of the platelet count of the group caplacizumab is shorter than the group placebo (SMD = -0.72; 95% CI -0.88 to -0.56; P  < 0.05). Caplacizumab reduced the incidence of mortality (OR = 0.41; 95% CI 0.18-0.92; P  < 0.05), exacerbations (OR = 0.10; 95% CI 0.05-0.18; P  < 0.05), and recurrence (OR = 0.17; 95% CI 0.06-0.50; P  < 0.05). However, the bleeding events in the caplacizumab group were higher than those in the placebo group, especially severe bleeding events. There was no difference in ADAMTS13 activity and thromboembolic events between the two groups. Our analysis indicated that caplacizumab is effective and well tolerated for the treatment of iTTP. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022362370.

Effect of omentopexy/gastropexy on gastrointestinal symptoms after laparoscopic sleeve gastrectomy: A meta-analysis of randomized controlled trials and systematic review.

INTRODUCTION: The increased prevalence of obesity worldwide and low incidence of postoperative complications make the laparoscopic sleeve gastrectomy (LSG) a clear public choice for obese-related individuals. Pre-existing studies reported contentious outcomes regarding the association with gastrointestinal symptoms after adding omentopexy (Ome) or gastropexy (Gas) to LSG. The present meta-analysis attempted to evaluate the pros and cons of operating Ome/Gas after LSG concerning gastrointestinal symptoms. METHODS: The data extraction and study quality assessment were independently performed by two individuals. The PubMed, EMBASE, Scopus, and Cochrane Library databases were systematically searched up to October 1, 2022, using the keywords LSG, omentopexy, and gastropexy to identify randomized controlled trial studies. RESULTS: Of the original 157 records, 13 studies with 3515 patients were included. LSG with Ome/Gas excels the LSG group in nausea (odds ratio [OR] = 0.57; 95% CI[0.46, 0.70]; P < .00001), reflux (OR = 0.57; 95% CI [0.46, 0.70]; P < .00001), vomiting (OR = 0.41; 95% CI [0.25, 0.67]; P = .0004) on gastrointestinal symptoms and bleeding (OR = 0.36; 95% CI [0.22, 0.59]; P < .0001), leakage (OR = 0.19; 95% CI [0.09, 0.43]; P < .0001), gastric torsion (OR = 0.23; 95% CI [0.07, 0.75]; P = .01) on post-LSG complications. Further, LSG with Ome/Gas was superior to LSG regarding the result of excess body mass index loss in 1 year after surgery (mean difference = 1.83; 95% CI [0.59, 3.07]; P = .004). However, no significant associations were shown between groups in wound infection and the resulting weight or body mass index 1 year after surgery. Of note, subgroup analysis indicated that gastroesophageal reflux disease can be alleviated by adding Ome/Gas post-LSG in those who used small bougies from 32 to 36 Fr (OR = 0.24; 95% CI [0.17, 0.34]; P < .00001) in contrast with large bougies over 36 Fr. CONCLUSION: Most results elucidated the impact of adding Ome/Gas after LSG in reducing the incidence of gastrointestinal symptoms. Additionally, more studies should be conducted to find the relations between other indicators in the present analysis due to the poor cases.

A meta-analysis: retrograde intrarenal surgery vs. percutaneous nephrolithotomy in children.

Backgrounds: The increasing prevalence of pediatric kidney stones worldwide makes minimally invasive lithotripsy like retrograde intrarenal surgery (RIRS) and percutaneous Nephrolithotomy (PCNL) more prevalent. However, their safety and efficacy are controversial. Consequently, a meta-analysis of the comparison between RIRS and PCNL is conducted. Methods: Clinical trials were selected from PubMed, EMBASE, Scopus, and Cochrane Library databases. The data extraction and study quality assessment were performed by two individuals independently. The data relating to therapeutic effects were extracted and analyzed by Review manager 5.4. Results: Thirteen studies involving 1,019 patients were included. The micro-PCNL excelled in stone-free rate (P = 0.003), postoperative fever rate (P = 0.02), and Clavien-Dindo II complications (P = 0.05). Notably, the mean age of the micro-PCNL group was younger than other groups (P = 0.0005). The operation time in mini-PCNL was longer than RIRS (P < 0.00001) but with high heterogeneity (I2 = 99%). There was no difference in Clavien-Dindo I, II, and III complications between the PCNL and the RIRS, but mini-PCNL showed a higher probability than RIRS in Clavien-Dindo I (P = 0.0008) and II complications (P = 0.007). Conclusions: Compared with RIRS, micro-PCNL could be a better therapeutic option for kidney stones in children. Of note, more parameters should be analyzed to illustrate the efficacy of different minimally invasive surgeries for pediatric kidney stones due to poor cases in our study. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/#recordDetails, PROSPERO CRD42022323611.

Epigallocatechin-3-gallate Induced HepG2 Cells Apoptosis through ROSmediated AKT /JNK and p53 Signaling Pathway.

BACKGROUND: Hepatocarcinoma is the third leading cause of cancer-related deaths around the world. Recently, some studies have reported that Epigallocatechin-3-gallate (EGCG) may have the anti-cancer potential. However, the affection and putative mechanisms of cytotoxicity induced by EGCG in HepG2 cells remain unknown. Based on the above, the present study evaluated the effect of EGCG on the cytotoxic and anti-cancer mechanisms of HepG2 cells. METHODS: The effect of EGCG on the apoptosis of Hep-G2 cells and its mechanism were studied by cell counting kit-8, mitochondrial membrane potential assay with JC-1, Annexin V-FITC apoptosis detection, cell cycle, and apoptosis analysis, one step TUNEL apoptosis assay, caspase 3 activity assay, caspase 9 activity Assay, Reactive Oxygen Species assay, and Western blot. RESULTS: EGCG-induced HepG2 cell apoptosis was confirmed by accumulation of the sub-G1 cells population, translocation of phosphatidylserine, depletion of mitochondrial membrane potential, DNA fragmentation, caspase-3 activation, caspase-9 activation, and poly (ADP-ribose) polymerase cleavage. Furthermore, EGCG enhanced cytotoxic effects on HepG2 cells and triggered intracellular reactive oxygen species; the signaling pathways of AKT, JNK, and p53 were activated to advance cell apoptosis. CONCLUSION: The results reveal that EGCG may provide useful information on EGCG-induced HepG2 cell apoptosis and be an appropriate candidate for cancer chemotherapy.

Closed or Unclosed Mesentery? A Meta-analysis of Internal Herniation After Laparoscopic Roux-en-Y Gastric Bypass.

During the laparoscopic Roux-en-Y gastric bypass procedure, closing mesentery or not was still controversial according to preexisted studies. So, the current meta-analysis aimed to compare the outcome of closure versus non-closure of mesenteric defects in laparoscopic Roux-en-Y gastric bypass. Fifteen studies were included, enrolling 53,488 patients. Based on the outcome of analysis, regarding internal hernia, Petersen space's IH, jejunal mesenteric's IH, hospital days, and reoperation, closure of the mesentery was better than non-closure. Besides, small bowel obstruction, anastomosis ulcer, stenosis, leakage, bleeding, gastrointestinal perforation, and postoperative BMI of patients show no difference between non-closure and closure.

Effects of dapagliflozin in the progression of atherosclerosis in patients with type 2 diabetes: a meta-analysis of randomized controlled trials.

AIMS: At present, an increasing number of studies are trying to determine whether dapagliflozin has a significant effect on the occurrence and development of atherosclerosis in patients with type 2 diabetes mellitus (T2DM), but there is no consensus. In addition, the former meta-analyses, relying on only a few previous studies and a minimal number of research indicators, have not been able to draw sufficient conclusions simultaneously. Consequently, we conducted a meta-analysis to evaluate the effectiveness of dapagliflozin in the occurrence and development of atherosclerosis in patients with T2DM. METHODS: We searched electronic databases (PubMed, Embase, Cochrane, and Scopus) and reference lists in relevant papers for articles published in 2011-2021. We selected studies that evaluated the effects of dapagliflozin on the risk factors related to the occurrence or development of atherosclerosis in patients with T2DM. A fixed or random-effect model calculated the weighted average difference of dapagliflozin on efficacy, and the factors affecting heterogeneity were determined by Meta-regression analysis. RESULTS: Twelve randomized controlled trials (18,758 patients) were incorporated in our meta-analysis. In contrast with placebo, dapagliflozin was associated with a significantly increase in high density lipoprotein-cholesterol (HDL-C) [MD = 1.39; 95% CI (0.77, 2.01); P < 0.0001], Δflow-mediated vasodilatation (ΔFMD) [MD = 1.22; 95% CI (0.38, 2.06); P = 0.005] and estimated Glomerular Filtration Rate(eGFR) [MD = 1.94; 95% CI (1.38, 2.51); P < 0.00001]. Furthermore, dapagliflozin had a tremendous advantage in controlling triglycerides (TG) in subgroups whose baseline eGFR < 83 ml/min/1.73m2 [MD = - 10.38; 95% CI (- 13.15, - 7.60); P < 0.00001], systolic blood pressure (SBP) [MD = - 2.82; 95% CI (- 3.22, - 2.42); P < 0.00001], HbA1c, BMI, body weight and waist circumference. However, dapagliflozin has an adverse effect on increasing total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C). Besides, there were no significant changes in other indicators, including adiponectin and C-peptide immunoreactivity. CONCLUSIONS: Our pooled analysis suggested that dapagliflozin has a terrifically better influence over HDL-C, ΔFMD, and eGFR, and it concurrently had a tremendous advantage in controlling TG, SBP, DBP, HbA1c, BMI, body weight, and waist circumference, but it also harms increasing TC and LDL-C. Furthermore, this study found that the effect of dapagliflozin that decreases plasma levels of TG is only apparent in subgroups of baseline eGFR < 83 ml/min/1.73m2, while the subgroup of baseline eGFR ≥ 83 ml/min/1.73m2 does not. Finally, the above results summarize that dapagliflozin could be a therapeutic option for the progression of atherosclerosis in patients with T2DM. Systematic review registration PROSPERO CRD42021278939.

Advances in metformin for the treatment of non-alcoholic fatty liver disease in children.

INTRODUCTION: The increased economic and social burdens for NAFLD worldwide make treating such a disease a significant public health issue. Metformin, a kind of insulin sensitizer generally used to treat type 2 diabetes, has been recently found to have efficacy on children's NAFLD in various areas such as glucolipid metabolism, intestinal bacterial metabolism, oxidative stress, and anti-inflammatory response. This article aims to provide an overview of the possible mechanisms of NAFLD in children and the potential therapeutic application of metformin. AREAS COVERED: The Cochrane Library, PubMed, Scopus, and EMBASE database was systematically searched on 12 April 2022, using the keywords metformin; non-alcoholic fatty liver disease; and children to identify similar studies. An additional search for recently published research was performed in June 2020. EXPERT OPINION: Although metformin has been proved to have an excellent therapeutic effect on children's NAFLD; we can still explore its potential impacts and mechanisms from different angles, such as combined medication. At the same time, we should also pay attention to its side effects.

Gankyrin sustains PI3K/GSK-3ß/ß-catenin signal activation and promotes colorectal cancer aggressiveness and progression.

High levels of angiogenesis, metastasis and chemoresistance are major clinical features of colorectal cancer (CRC), a lethal disease with a high incidence worldwide. Aberrant activation of Wnt/ß-catenin pathway contributes to CRC progression. However, little is known about regulatory mechanisms of the ß-catenin activity in cancer progression. Here we report that Gankyrin was markedly upregulated in primary tumor tissues from CRC patients and was associated with poor survival. Moreover, we demonstrated that overexpressing Gankyrin promoted, while knockdown of Gankyrin impaired, the aggressive phenotype of proliferation, angiogenesis, chemoresistance and metastasis of CRC cells both in vitro and in vivo. Importantly, we found a unique molecular mechanism of Gankyrin in CRC cells signaling transduction, that regulated the cross-talk between PI3K/Akt and Wnt/ß-catenin signaling pathways, sustaining PI3K/GSK-3ß/ß-catenin signal activation in CRC. Therefore, these findings not only reveal a mechanism that promotes aggressiveness and progression in CRC, but also provide insight into novel molecular targets for antitumor therapy in CRCs.

[Association of gankyrin protein expression in human colorectal cancer with postoperative prognosis].

OBJECTIVE: To investigate the association of gankyrin protein expression in colorectal cancer (CRC) with its prognosis. METHODS: Clinical data and resection samples of 100 colorectal cancer patients identified by pathology undergoing resection in our department from June 2008 to June 2009 were collected. The gankyrin expression in CRC tissues and matched adjacent noncancerous tissues collected during the operation of 100 CRC cases was detected by immunohistochemical staining and Western blotting. The associations of gankyrin expression level with overall survival, clinicopathologic features were analyzed by Chi square test, Cox regression analysis, Kaplan-Meier analysis and log rank test. RESULTS: Immunohistochemical staining showed that the positive brown granules were mainly distributed in the cytoplasm, and nuclear immunostaining was observed in tissue samples of 29 cases, of whom 16 cases had distal metastasis [55.2% (16/29)]. The positive rate of gankyrin and the relative gray value of Western blotting in CRC tissues were 67% (67/100) and 0.69±0.23, respectively, which were significantly higher than those of 2 cm adjacent noncancerous tissues [6% (6/100) and 0.31±0.16] and 10 cm adjacent noncancerous tissues [1%(1/100) and 0.16±0.11] (all P<0.001). Patients with positive expression of gankyrin had worse survival than those with negative ones (41.8% vs. 72.7%, P=0.008). The gankyrin expression was associated to lymph node metastasis (P=0.005), tumor stage (P=0.001) and distal metastasis (P=0.002). Cox regression analysis showed that distal metastasis (P=0.004) and high expression of gankyrin (P=0.038) were independent risk factors for poor prognosis of patients with CRC. CONCLUSION: Up-regulated expression of gankyrin is related to invasion and metastasis of human CRC, and gankyrin may be valuable in predicting prognosis.