LncRNA GAS5 upregulates Smad4 to suppress the apoptosis of chondrocytes induced by lipopolysaccharide

Background: Osteoarthritis (OA) is closely correlated with inflammation. It has been reported that lncRNA GAS5 plays an important role in inflammation, indicating the potential involvement of GAS5 in OA. This study was carried out to investigate the function of GAS5 in OA.Methods: Expression levels of GAS5 in synovial fluid from 45 OA patients and 45 healthy controls were measured by RT-qPCR. Cell transfections were performed to explore the potential interactions among GAS5, miR-146a, and Smad4 in chondrocytes. Lipopolysaccharide (LPS)-induced cell apoptosis after overexpression of GAS5, miR-146a, and Smad4 was analyzed by cell apoptosis assay.Results: GAS5 was downregulated in OA. Moreover, LPS treatment downregulated GAS5 in chondrocytes. Interaction between GAS5 could with miR-146a was predicted by bioinformatics analysis and further confirmed by RNA-RNA pulldown assay. However, overexpression of GAS5 and miR-146a did not affect the expression of each other. GAS5 overexpression increased Smad4 expression in chondrocytes. In contrast, miR-146a overexpression downregulated Smad4 in chondrocytes. Moreover, GAS5 and Smad4 overexpression inhibited LPS- induced chondrocytes apoptosis, while miR-146a overexpression played an opposite role and attenuated the effects of GAS5 and Smad4 overexpression on cell apoptosis.Conclusion: GAS5 might sponge miR-146a to upregulate Smad4, thereby suppressing LPS- induced chondrocytes apoptosis.     

Potentilla anserine L. polysaccharide protects against cadmium-induced neurotoxicity

Cadmium is a toxic metal that can damage the brain and other organs. This study aimed to explore the protective effects of Potentilla anserine L. polysaccharide (PAP) against CdCl₂-induced neurotoxicity in N2a and SH-SY5Y cells and in the cerebral cortex of BALB/c mice. In addition, we aimed to identify the potential mechanisms underlying these protective effects. Relative to CdCl₂ treatment alone, pretreatment with PAP prevented the reduction in cell viability evoked by CdCl₂, decreased rates of apoptosis, promoted calcium homeostasis, decreased ROS accumulation, increased mitochondrial membrane potential, inhibited cytochrome C and AIF release, and prevented the cleavage of caspase-3 and PARP. In addition, PAP significantly decreased the CdCl₂-induced phosphorylation of CaMKII, Akt, and mTOR. In conclusion, PAP represents a potential therapeutic agent for the treatment of Cd-induced neurotoxicity, functioning in part via attenuating the activation of the mitochondrial apoptosis pathway and the Ca²⁺-CaMKII-dependent Akt/mTOR pathway.     

Impact of different types of olive oil on cardiovascular risk factors: A systematic review and network meta-analysis

Background and aimThis network meta-analysis (NMA) compares the effects of different types of olive oil (OO) on cardiovascular risk factors.Methods and resultsLiterature search was conducted on three electronic databases (Medline, Web of Science, and Cochrane Central). Inclusion criteria: Randomized controlled trials (RCTs) (≥3 weeks duration of intervention) comparing at least two of the following types of OO: refined OO (ROO), mixed OO (MOO), low phenolic (extra) virgin OO (LP(E)VOO), and high phenolic (extra) virgin OO (HP(E)VOO). Random-effects NMA was performed for seven outcomes; and surface under the cumulative ranking curve (SUCRA) was estimated, using an analytical approach (P-score). Thirteen RCTs (16 reports) with 611 mainly healthy participants (mean age: 26–70 years) were identified. No differences for total cholesterol, HDL-cholesterol, triacylglycerols, and diastolic blood pressure were observed comparing ROO, MOO, LP(E)VOO and HP(E)VOO. HP(E)VOO slightly reduce LDL-cholesterol (LDL-C) compared to LP(E)VOO (mean difference [MD]: −0.14 mmol/L, 95%–CI: −0.28, −0.01). Both, HP(E)VOO and LP(E)VOO reduces SBP compared to ROO (range of MD: −2.99 to −2.87 mmHg), and HP(E)VOO may improve oxidized LDL-cholesterol (oxLDL-C) compared to ROO (standardized MD: −0.68, 95%–CI: −1.31, −0.04). In secondary analyses, EVOO may reduce oxLDL-C compared to ROO, and a dose-response relationship between higher intakes of phenolic compounds from OO and lower SBP and oxLDL-C values was detected. HP(E)VOO was ranked as best treatment for LDL-C (P-score: 0.83), oxLDL-C (0.88), and SBP (0.75).ConclusionsHP(E)VOO may improve some cardiovascular risk factors, however, public health implications are limited by overall low or moderate certainty of evidence.     

Self-reported outcomes of a randomized trial comparing three community health worker interventions for diabetes prevention among Cambodian Americans with depression

ObjectiveCambodian Americans have complex, interrelated and persistent medical and mental health problems stemming from genocide and the social determinants of health. We examined changes in multiple domains of self-reported health outcomes from a diabetes prevention trial. Methods: Cambodian Americans with depression and high risk for diabetes (n = 188) were randomized to one of three community health worker interventions: lifestyle vs lifestyle plus medication therapy management vs social services. Assessments were at baseline, 12- and 15-months. Results: The typical participant was 55 years old, female, earned below $20,000 annually, and had 7 years of education. About one-third were taking antidepressant medication and over half had elevated depressive symptoms. Relative to social services, lifestyle and lifestyle plus medication therapy management were both similarly effective at increasing diabetes knowledge, nutrition habits, sleep quality and decreasing pain; 2) lifestyle alone was superior to social services for self-reported health; and, 3) all three groups showed improved anxiety and insomnia. There were no effects on physical activity or physical functioning. Conclusion: Community health worker interventions have multiple benefits beyond delaying diabetes. Practice Implications: Health promotion programs that are designed and delivered appropriately can impact even hard to reach and hard to treat groups.     

The mucosal immune system of the upper respiratory tract and recent progress in mucosal vaccines

The mucosal immune system prevents microorganism invasion through mucosal surfaces and consists of inductive and effector sites. Nasopharynx-associated lymphoid tissue (NALT) functions as an inductive site, inducing mucosal immune responses in the upper respiratory tract. It follows that intranasal vaccines may prevent upper respiratory infections. To induce and enhance the immune response by administering inactivated antigens intranasally, mucosal adjuvants have been developed, including mutant cholera toxin and cationic cholesteryl pullulan nanogel, which do not accumulate in the central nervous system. Moreover, multivalent pneumococcal polysaccharide conjugate vaccines are used to prevent invasive pneumococcal infections and otitis media, although they only provide moderate protection against acute otitis media because non-vaccine serotypes of Streptococcus pneumoniae and Haemophilus influenzae also cause this infection. To address this problem, pneumococcal surface protein A of S. pneumoniae and P6 of H. influenzae are used as broad-spectrum vaccine antigens. Alternatively, phosphorylcholine (PC) is present in the cell walls of both gram-positive and gram-negative bacteria and induces immune responses through antigenic activity. The significant effects of PC as a mucosal vaccine have been demonstrated through intranasal and sublingual immunization in mice. Furthermore, intranasal administration of PC reverses increases in IgE levels and prevents allergic rhinitis. After immunization with pneumococcal polysaccharide conjugate vaccine, intranasal immunization with PC boosts immune responses to vaccine strains and to PC itself. Thus, PC may be useful as a mucosal vaccine to prevent upper respiratory infections and allergic rhinitis, and it could be used as a booster to the currently used pneumococcal vaccine as it protects against non-vaccine strains.     

Bio-accumulation and health risk assessment of heavy metals in different edible fish species from Hurghada City,Red Sea,Egypt

BackgroundHeavy metal contamination has become a serious issue in this century especially detected in fish organs. Due to the presence of radioactive compounds in agricultural and sewage effluent, which destroys aquatic ecosystems, threatening human livelihoods. Health hazards associated with low and high consumption consumers assessed in five commercial fish species collected from Hurghada City, Egypt, during winter and summer, 2020. Atomic absorption spectrophotometer technique used for determination heavy meals in different organs and expressed as μg/g wet weight.ResultsHeavy metal concentrations in muscle ranged between:(0.054–0.109), (0.260–1.043), (0.264–0.897), (5.895–11.898), (0.381–0.970), (13.582–29.133) and (0.332–0.589) µg/g for Cd, Pb, Mn, Zn, Cu, Fe and Ni respectively, which were lower than those of gills and liver. These concentrations were within WHO, FAO/WHO, and EU standards. Consumption of edible species was lower than the (TDIs) established by the (JECFA) and Egyptian Standards. Even though THQ and TTHQ values were < 1 while, in children with highly consumer were> 1.ConclusionThis study concluded that intake of Red Sea fish is safe for human health. It is critical for consumers to be aware of the consequences of excessive fish consumption, particularly children with highly consumer, which represent possible health risks.     

Combining CAPRA-S With Tumor IDC/C Features Improves the Prognostication of Biochemical Recurrence in Prostate Cancer Patients

Background: Intraductal carcinoma and cribriform (IDC/C) tumor features are well-established prognosticators of biochemical recurrence (BCR), metastasis, and prostate cancer (PCa)-specific mortality. However, approximately 70% of PCa patients undergoing a radical prostatectomy are IDC/C negative, yet up-to 20% of these patients progress and experience BCR. Thus, tumor histopathologic characteristics such as IDC/C alone are limited in their ability to predict disease progression. Conversely, several nomograms such as Cancer of the Prostate Risk Assessment-Surgery (CAPRA-S) have been developed to aid in the prognostication of BCR, but not yet widely applied in clinical settings. Materials and methods: In this study, we assessed the combined prognostic utility of IDC/C, and CAPRA-S for BCR in 3 PCa patient cohorts. Results: CAPRA-S+IDC/C improved the predictive accuracy of BCR in all 3 cohorts (P < .001). Specifically, among IDC/C negative cases, CAPRA-S improved the prognostication of BCR in low-risk (Cohort 1; P < .001, Cohort 2; P < .001, Cohort 3; P = .003), intermediate (Cohort 1; P < .001, Cohort 2; P = .006, Cohort 3; P = .03) and high-risk (Cohort 1-3; P < .001) patients. Conversely, IDC/C improved the prognostication of BCR among CAPRA-S low-risk (Cohorts 1; P < .001 and Cohort 3; P = .003) patients. Conclusion: Our results suggest the investigation of histopathological IDC/C features in CAPRA-S low-risk patients and conversely, nomogram CAPRA-S among IDC/C negative patients improves the identification of patients likely to experience BCR, which would otherwise be missed through current assessment regimens. These patients can be offered more intensive monitoring and adjuvant therapies upfront to circumvent the development of recurrent cancer or overtreatment at the time of surgery.     

Association of kidney function with cancer incidence and its influence on cancer risk of smoking: The Japan Multi-Institutional Collaborative Cohort Study

The association between kidney function and cancer incidence is inconsistent among previous reports, and data on the Japanese population are lacking. It is unknown whether kidney function modifies the cancer risk of other factors. We aimed to evaluate the association of estimated glomerular filtration rate (eGFR) with cancer incidence and mortality in 55 242 participants (median age, 57 years; 55% women) from the Japan Multi-Institutional Collaborative Cohort Study. We also investigated differences in cancer risk factors between individuals with and without kidney dysfunction. During a median 9.3-year follow-up period, 4278 (7.7%) subjects developed cancer. Moderately low and high eGFRs were associated with higher cancer incidence; compared with eGFR of 60-74 ml/min/1.73 m², the adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) for eGFRs of ≥90, 75-89, 45-59, 30-44 and 10-29 ml/min/1.73 m² were 1.18 (1.07-1.29), 1.09 (1.01-1.17), 0.93 (0.83-1.04), 1.36 (1.00-1.84) and 1.12 (0.55-2.26), respectively. High eGFR was associated with higher cancer mortality, while low eGFR was not; the adjusted subdistribution HRs (95% CIs) for eGFRs of ≥90 and 75-89 ml/min/1.73 m² were 1.58 (1.29-1.94) and 1.27 (1.08-1.50), respectively. Subgroup analyses of participants with eGFRs ≥60 and <60 ml/min/1.73 m² revealed elevated cancer risks of smoking and family history of cancer in those with eGFR <60 ml/min/1.73 m², with significant interactions. Our findings suggest that the relationship between eGFR and cancer incidence was U-shaped. Only high eGFR was associated with cancer mortality. Kidney dysfunction enhanced cancer risk from smoking.