The effect of celastrol in combination with 5-fluorouracil on proliferation and apoptosis of gastric cancer cell lines.

Background: Despite the availability of chemotherapy drugs such as 5-fluorouracil (5-FU), the treatment of some cancers such as gastric cancer remains challenging due to drug resistance and side effects. This study aimed to investigate the effect of celastrol in combination with the chemotherapy drug 5-FU on proliferation and induction of apoptosis in human gastric cancer cell lines (AGS and EPG85-257). Materials and Methods: In this in vitro study, AGS and EPG85-257 cells were treated with different concentrations of celastrol, 5-FU, and their combination. Cell proliferation was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The synergistic effect of 5-FU and celastrol was studied using Compusyn software. The DNA content at different phases of the cell cycle and apoptosis rate was measured using flow cytometry. Results: Co-treatment with low concentrations (10% inhibitory concentration (IC10)) of celastrol and 5-FU significantly reduced IC50 (p < 0.05) so that 48 h after treatment, IC50 was calculated at 3.77 and 6.9 µM for celastrol, 20.7 and 11.6 µM for 5-FU, and 5.03 and 4.57 µM for their combination for AGS and EPG85-257 cells, respectively. The mean percentage of apoptosis for AGS cells treated with celastrol, 5-FU, and their combination was obtained 23.9, 41.2, and 61.9, and for EPG85-257 cells 5.65, 46.9, and 55.7, respectively. In addition, the 5-FU and celastrol-5-FU combination induced cell cycle arrest in the synthesis phase. Conclusions: Although celastrol could decrease the concentration of 5-fluorouracil that sufficed to suppress gastric cancer cells, additional studies are required to arrive at conclusive evidence on the anticancer effects of celastrol.

Gender-Affirming Hormone Treatment and Metabolic Syndrome Among Transgender Veterans.

Importance: Gender-affirming hormone treatment (GAHT) is a common therapy for transgender individuals to reduce gender dysphoria and improve quality of life. Clarifying the long-term effects of GAHT remains a priority in transgender health research. Objective: To explore whether sex hormones (estradiol and testosterone) are associated with the development of metabolic syndrome in transgender veterans compared with cisgender veterans. Design, Setting, and Participants: This retrospective, longitudinal cohort study used International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnosis codes for gender dysphoria from the Veterans Health Administration national database to identify transfeminine and transmasculine veterans receiving documented feminizing (estradiol) or masculinizing (testosterone) treatment from January 1, 2006, to December 31, 2019, and for whom the GAHT initiation date and metabolic syndrome component-related data were available. Transgender veterans were matched to cisgender referents. Exposure: Gender-affirming hormone treatment. Main Outcomes and Measures: Metabolic syndrome z-scores were calculated based on body mass index, systolic blood pressure, and levels of high-density lipoprotein cholesterol, triglycerides, and blood glucose. Changes in mean z-scores were compared among the transgender and cisgender groups before and after the index date (corresponding to GAHT initiation) using a repeated-measures analysis of variance model. Results: The cohort included 1290 participants: 645 transgender (494 [38.3%] transfeminine, 151 [11.7%] transmasculine) and 645 cisgender (280 [21.7%] female, 365 [28.3%] male). Mean (SD) age at the index date was 41.3 (13.2) years. Metabolic syndrome z-scores changed significantly over time and differed significantly across groups. Overall, transmasculine veterans had the greatest percentage increase in mean (SEM) z-scores after vs before the index date (298.0% [57.0%]; P < .001), followed by cisgender females (108.3% [27.5%]; P < .001), cisgender males (49.3% [27.5%]; P = .02), and transfeminine persons (3.0% [10.7%]; P = .77). Conclusions and Relevance: In this cohort study, in both cisgender and transgender veterans, estradiol was associated with reduced metabolic syndrome risk, whereas testosterone was associated with increased risk. However, transmasculine individuals had the greatest risk and transfeminine individuals had the lowest risk of metabolic syndrome associated with these hormones. This is relevant for the management of metabolic syndrome risk factors in cisgender and transgender individuals and to potentially predict the risk of atherosclerotic cardiovascular disease, type 2 diabetes, systolic hypertension, insulin resistance, and nonalcoholic fatty liver disease.

Serum Low-Density Lipoprotein Cholesterol and Cardiovascular Disease Risk Across Chronic Kidney Disease Stages (Data from 1.9 Million United States Veterans).

In the general population, elevated low-density lipoprotein (LDL) cholesterol levels are an important risk factor for cardiovascular disease (CVD) and mortality; however, the association of LDL with mortality risk and cardiovascular events are less clear in chronic kidney disease (CKD). We sought to examine the relationship of LDL with mortality and rates of atherosclerotic cardiovascular disease (ASCVD) and non-atherosclerotic cardiovascular-related (non-ASCVD) hospitalizations across CKD stages. Our analytical cohort consisted of 1,972,851 United States veterans with serum LDL data between 2004 and 2006. Associations of LDL with all-cause and cardiovascular mortality across CKD stages were evaluated using Cox proportional hazard models with adjustment for demographics, comorbid conditions, smoking status, prescription of statins and non-statin lipid-lowering drugs, body mass index, albumin, high-density lipoprotein, and triglycerides. Associations between LDL and ASCVD and non-ASCVD hospitalizations were estimated using negative binomial regression models across CKD stages. The cohort consisted of 5% female, 14% Black, 29% diabetic, 33% statin-users, and 44% current smokers, with a mean patient age of 64 ± 14 years. Patients with high LDL (≥160 mg/dL) had a higher risk of all-cause and cardiovascular mortality as well as ASCVD and non-ASCVD hospitalization rates across all CKD stages compared with the reference (LDL 70 to <100 mg/dL). The associations with all-cause and cardiovascular mortality and ASCVD hospitalization rate were attenuated at higher CKD stages. These trends were reversed with amplification of the association of high LDL with non-ASCVD hospitalization at higher CKD stages. In conclusion, associations of LDL with mortality and both ASCVD and non-ASCVD hospitalizations are modified according to kidney disease stage.

The quest for cardiovascular disease risk prediction models in patients with nondialysis chronic kidney disease.

PURPOSE OF REVIEW: Cardiovascular disease (CVD) is the leading cause of death in patients with chronic kidney disease (CKD). However, traditional CVD risk prediction equations do not work well in patients with CKD, and inclusion of kidney disease metrics such as albuminuria and estimated glomerular filtration rate have a modest to no benefit in improving prediction. RECENT FINDINGS: As CKD progresses, the strength of traditional CVD risk factors in predicting clinical outcomes weakens. A pooled cohort equation used for CVD risk prediction is a useful tool for guiding clinicians on management of patients with CVD risk, but these equations do not calibrate well in patients with CKD, although a number of studies have developed modifications of the traditional equations to improve risk prediction. The reason for the poor calibration may be related to the fact that as CKD progresses, associations of traditional risk factors such as BMI, lipids and blood pressure with CVD outcomes are attenuated or reverse, and other risk factors may become more important. SUMMARY: Large national cohorts such as the US Veteran cohort with many patients with evolving CKD may be useful resources for the developing CVD prediction models; however, additional considerations are needed for the unique composition of patients receiving care in these healthcare systems, including those with multiple comorbidities, as well as mental health issues, homelessness, posttraumatic stress disorders, frailty, malnutrition and polypharmacy. Machine learning over conventional risk prediction models may be better suited to handle the complexity needed for these CVD prediction models.

A Case-Based Review of Iron Overload With an Emphasis on Porphyria Cutanea Tarda, Hepatitis C, C282Y Heterozygosity, and Coronary Artery Disease.

Iron overload can impact disease progression and treatment options for patients with comorbid conditions, such as porphyria cutanea tarda, hepatitis C virus, and coronary artery disease.

Anti-adenovirus activity, antioxidant potential, and phenolic content of black tea (Camellia sinensis Kuntze) extract.

BackgroundAdenovirus (ADV) causes a number of diseases in human, and to date, no specific antiviral therapy is approved against this virus. Thus, searching for effective anti-ADV agents seems to be an urgent requirement. Many studies have shown that components derived from medicinal plants have antiviral activity. Therefore, the present study was aimed to evaluate in vitro anti-ADV activity and also antioxidant potential and total phenolic compounds of black tea (Camellia sinensis) crude extract. MethodsIn this study, the hydroalchoholic extract of black tea was prepared and its anti-ADV activity was evaluated on HEp2 cell line using MTT [3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide] assay. The 50 % inhibitory concentration (IC50) and 50 % cytotoxicity concentration (CC50) of the extract were determined using regression analysis. Its inhibitory effect on adsorption and/or post-adsorption stages of the virus replication cycle was evaluated. To determine antioxidant activity, total phenol content, and flavonoids content of the extract, the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, Folin-Ciocalteu method, and aluminum chloride colorimetric method were used, respectively. ResultsThe CC50 and the IC50 of the extract were 165.95±12.7 and 6.62±1.4 µg/mL, respectively, with the selectivity index (SI) of 25.06. This extract inhibited ADV replication in post-adsorption stage. The IC50 of DPPH radical was 8±1.41 µg/mL, compared with butylated hydroxytoluene, with IC50 of 25.41±1.89 µg/mL. The total phenol and flavonoid contents of the extract were 341.8±4.41 mg gallic acid equivalent per gram and 21.1±2.11 mg/g, respectively. ConclusionsHaving SI value of 25.06 with inhibitory effect on ADV replication, particularly during the post-adsorption period, black tea extract could be considered as a potential anti-ADV agent. The antiviral activity of this extract could be attributed to its phenolic compounds.

Pheochromocytoma after Cesarean Section.

Pheochromocytoma is a catecholamine-producing tumor. There are a very few reported cases of clinical pheochromocytoma. Here, we report a 27-year-old woman para 1 live 1 with chief complaint of headache, confusion, nausea, and vomiting 2 days after cesarean section. She was anxious and had palpitation. On physical examination, fever, tachycardia, tachypnea, high blood pressure, and right thyroid nodule were found. She was managed as pregnancy-induced hypertension at first. In laboratory data, epinephrine, norepinephrine, metanephrine, normetanephrine, and vanillylmandelic acid were increased in 24 h urine collection. An adrenal mass was detected in abdominal computed tomography. Regarding clinical and paraclinical findings, pheochromocytoma was diagnosed. The patient received medical treatment, but it was not effective; hence, she underwent adrenalectomy.

Long-Term Survival of a Patient With Late-Stage Non-Small Cell Lung Cancer.

After not responding to chemotherapy and monoclonal antibody therapy, a patient with late-stage non-small cell lung cancer benefited from treatment with erlotinib.

A case of placental polyp after normal vaginal delivery.

Placental polyp is retained placental tissue within the endometrial cavity, which forms a nidus for inflammation and bleeding. There are very few reported cases of the clinical placental polyp. Here, we report a case of 34-year-old G4L3Ab1 woman with the chief complaint of intermittent vaginal bleeding since her last normal vaginal delivery 3 months ago. Serum human chorionic gonadotropin (hCG) titer was slightly elevated. A polypoid mass was detected within the endometrial cavity by imaging studies. History of the patient, mass lesion within the endometrial cavity and slightly elevated serum hCG titer raised the suspicion of trophoblastic neoplasms. Endometrial curettage yielded unsatisfactory specimen containing only fibrin deposition and was followed by total hysterectomy. The uterus showed slight global enlargement resulting from the presence of a polypoid mass within the endometrial cavity. The red-colored mass had a smooth outer surface and fragile consistency without any permeation into the myometrium. Pathology reported it as the placental polyp. Although very rare, placental polyp should be kept in mind as one of the reasons of abnormal uterine bleeding in parous women. Definite diagnosis is made by pathology examination.

Protective effect of caffeine against neurodegeneration in a model of Parkinson's disease in rat: behavioral and histochemical evidence.

Epidemiological studies have consistently demonstrated an inverse association between coffee consumption and Parkinson's disease (PD). This study was designed to investigate the beneficial effect of caffeine at a dose comparable to that of human exposure in a model of PD. For this purpose, unilateral intrastriatal 6-hydroxydopamine (6-OHDA)-lesioned rats were pretreated with caffeine (20 mg/kg; i.p.) 1 h before surgery and treated twice a day (10 mg/kg) for 1 month. Apomorphine-induced rotations and number of Nissl-stained neurons of substantia nigra pars compacta (SNC) were counted. The results demonstrated that caffeine administration for 1 month could attenuate the rotational behavior in lesioned rats and protect the neurons of SNC against 6-OHDA toxicity.