Malignant function of nuclear factor-kappaB axis in prostate cancer: Molecular interactions and regulation by non-coding RNAs.

Prostate carcinoma is a malignant situation that arises from genomic alterations in the prostate, leading to changes in tumorigenesis. The NF-κB pathway modulates various biological mechanisms, including inflammation and immune responses. Dysregulation of NF-κB promotes carcinogenesis, including increased proliferation, invasion, and therapy resistance. As an incurable disease globally, prostate cancer is a significant health concern, and research into genetic mutations and NF-κB function has the efficacy to facilitate the introduction of novel therapies. NF-κB upregulation is observed during prostate cancer progression, resulting in increased cell cycle progression and proliferation rates. Additionally, NF-κB endorses resistance to cell death and enhances the capacity for metastasis, particularly bone metastasis. Overexpression of NF-κB triggers chemoresistance and radio-resistance, and inhibition of NF-κB by anti-tumor compounds can reduce cancer progression. Interestingly, non-coding RNA transcripts can regulate NF-κB level and its nuclear transfer, offering a potential avenue for modulating prostate cancer progression.

The cardioprotective effects of cerium oxide nanoparticles against the poisoning generated by aluminum phosphide pesticide: Controlling oxidative stress and mitochondrial damage.

BACKGROUND: Aluminum phosphide (AlP) is a well-known toxic compound used as an agricultural pesticide to prevent insect damage to stored crops. However, even if just a small amount was consumed, it caused lasting harm to the human body and, in acute concentrations, death. The current study employed cerium oxide nanoparticles (CeO2 NPs) to reduce oxidative stress and various harmful outcomes of AlP poisoning. METHODS: Following finding effective concentrations of CeO2 NPs via MTT assay, Human Cardiac Myocyte (HCM) cells were pre-treated with CeO2 NPs for 24 h. After that, they were exposed to 2.36 µM AlP. The activity of oxidative stress and mitochondrial biomarkers, including mitochondrial swelling, mitochondrial membrane potential, and cytochrome c release, were evaluated in HCM cells. Finally, the population of apoptotic and necrotic cells was assessed via flow cytometry. RESULTS: After 24 h, data revealed that all tested concentrations of CeO2 NPs were safe, and 25 and 50 µM of that were selected as effective concentrations. Oxidative stress markers (malondialdehyde, protein carbonyl, superoxide dismutase, and catalase) showed that CeO2 NPs could successfully decrease AlP poisoning due to their antioxidant characteristics. Mitochondrial markers were also recovered by pre-treatment of HCM cells with CeO2 NPs. Furthermore, pre-treating with CeO2 NPs could compensate for the reduction of live cells with AlP and cause a diminishing in the population of early and late apoptotic cells. CONCLUSION: As a result, it is evident that CeO2 NPs, through the recovery of oxidative stress and mitochondrial damages caused by AlP, reduce apoptosis and have therapeutic potentials on HCM cells.

Resistance Training to Muscle Failure with Variable Load Intensities: Implications for Post-Exercise Blood Pressure and Heart Rate Variability in Trained Men.

Background: The modulation of cardiac sympathovagal balance alters following acute resistance training (RT) sessions. Nevertheless, the precise influence of RT at varying load intensities on this physiological response remains to be fully elucidated. Therefore, the aim of this study was to compare the time course of recovery following low- (40%), moderate- (60%), and high- (80%) load-intensity RT protocols performed up to muscle repetition failure in resistance-trained men. Method: Sixteen young, resistance-trained men (mean age: 21.6 ± 2.5 years, mean height: 175.7 ± 8.9 cm, mean weight: 77.1 ± 11.3 kg) participated in a randomized crossover experimental design involving three sessions, each taken to the point of muscle failure. These sessions were characterized by different load intensities: low (40% of 1-repetition maximum, 1RM), moderate (60% of 1RM), and high (80% of 1RM). The exercise regimen comprised four exercises-back squat (BS), bench press (BnP), barbell row (BR), and shoulder press (SP)-with each exercise consisting of three sets. Throughout each session, heart rate variability (HRV) and blood pressure (BP) parameters were assessed both pre-exercise and during a 40 min post-exercise period, segmented into 10 min intervals for stabilization. Statistical analysis involved the use of a repeated measures ANOVA. Results: It was observed that the 40% and 60% RT sessions resulted in a significantly higher root mean square of successive R-R intervals (RMSSD) value compared to the 80% RT session in the post-exercise recovery process in 30 min (respectively, p = 0.025; p = 0.028) and 40 min (respectively, p = 0.031; p = 0.046), while the 40% and 60% RT sessions produced similar responses. The 40% RT session was significantly higher in the high frequency (HF) value post-exercise in 40 min compared to the 80% RT session (p = 0.045). Conclusions: Our findings suggest that engaging in resistance training (RT) sessions to muscle failure at an intensity of 80% induces acute increases in sympathetic activity, potentially leading to elevated cardiovascular stress. For individuals with normal blood pressure, it is advisable to opt for lighter loads and higher repetition volumes when prescribing RT, as heavier-load RT may carry an increased risk of cardiac-related factors.

Targeting STAT3 signaling pathway by curcumin and its analogues for breast cancer: A narrative review.

BACKGROUND: Breast cancer (BC) continues to be a significant global health issue, with a rising number of cases requiring ongoing research and innovation in treatment strategies. Curcumin (CUR), a natural compound derived from Curcuma longa, and similar compounds have shown potential in targeting the STAT3 signaling pathway, which plays a crucial role in BC progression. AIMS: The aim of this study was to investigate the effects of curcumin and its analogues on BC based on cellular and molecular mechanisms. MATERIALS & METHODS: The literature search conducted for this study involved utilizing the Scopus, ScienceDirect, PubMed, and Google Scholar databases in order to identify pertinent articles. RESULTS: This narrative review explores the potential of CUR and similar compounds in inhibiting STAT3 activation, thereby suppressing the proliferation of cancer cells, inducing apoptosis, and inhibiting metastasis. The review demonstrates that CUR directly inhibits the phosphorylation of STAT3, preventing its movement into the nucleus and its ability to bind to DNA, thereby hindering the survival and proliferation of cancer cells. CUR also enhances the effectiveness of other therapeutic agents and modulates the tumor microenvironment by affecting tumor-associated macrophages (TAMs). CUR analogues, such as hydrazinocurcumin (HC), FLLL11, FLLL12, and GO-Y030, show improved bioavailability and potency in inhibiting STAT3, resulting in reduced cell proliferation and increased apoptosis. CONCLUSION: CUR and its analogues hold promise as effective adjuvant treatments for BC by targeting the STAT3 signaling pathway. These compounds provide new insights into the mechanisms of action of CUR and its potential to enhance the effectiveness of BC therapies.

A Systematic Review of the Chemo/Radioprotective Effects of Melatonin against Ototoxic Adverse Effects Induced by Chemotherapy and Radiotherapy.

BACKGROUND: Although chemotherapy and radiotherapy are effective in cancer treatment, different adverse effects induced by these therapeutic modalities (such as ototoxicity) restrict their clinical use. Co-treatment of melatonin may alleviate the chemotherapy/radiotherapy-induced ototoxicity. OBJECTIVE: In the present study, the otoprotective potentials of melatonin against the ototoxicity induced by chemotherapy and radiotherapy were reviewed. METHODS: According to the PRISMA guideline, a systematic search was carried out to identify all relevant studies on "the role of melatonin against ototoxic damage associated with chemotherapy and radiotherapy" in the different electronic databases up to September 2022. Sixty-seven articles were screened based on a predefined set of inclusion and exclusion criteria. Seven eligible studies were finally included in this review. RESULTS: The in vitro findings showed that cisplatin chemotherapy significantly decreased the auditory cell viability compared to the control group; in contrast, the melatonin co-administration increased the cell viability of cisplatin-treated cells. The results obtained from the distortion product otoacoustic emission (DPOAE) and auditory brainstem response (ABR) tests demonstrated a decreased amplitude of DPOAE and increased values of ABR I-IV interval and ABR threshold in mice/rats receiving radiotherapy and cisplatin; nevertheless, melatonin co-treatment indicated an opposite pattern on these evaluated parameters. It was also found that cisplatin and radiotherapy could significantly induce the histological and biochemical changes in the auditory cells/tissue. However, melatonin co-treatment resulted in alleviating the cisplatin/radiotherapy-induced biochemical and histological changes. CONCLUSION: According to the findings, it was shown that melatonin co-treatment alleviates the ototoxic damage induced by chemotherapy and radiotherapy. Mechanically, melatonin may exert its otoprotective effects via its anti-oxidant, anti-apoptotic, and anti-inflammatory activities and other mechanisms.

NLRP3 inflammasome pathway in atherosclerosis: Focusing on the therapeutic potential of non-coding RNAs.

NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) inflammasome pathway has a critical role in the pathogenesis of atherosclerosis. Activation of this pathway is implicated in the subendothelial inflammation and atherosclerosis progression. The NLRP3 inflammasome are cytoplasmic sensors with the distinct capacity to identify a wide range of inflammation-related signals, which enhance NLRP3 inflammasome assembly and allow it to trigger inflammation. This pathway is triggered by a variety of intrinsic signals which exist in atherosclerotic plaques, like cholesterol crystals and oxidized LDL. Further pharmacological findings indicated that NLRP3 inflammasome enhanced caspase-1-mediated secretion of pro-inflammatory mediators like interleukin (IL)- 1ß/18. Newly published cutting-edge studies suggested that non-coding RNAs (ncRNAs) including microRNAs (miRNAs, miRs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) are major modulators of NLRP3 inflammasome in atherosclerosis. Therefore, in this review, we aimed to discuss the NLRP3 inflammasome pathway, biogenesis of ncRNAs as well as the modulatory role of ncRNAs in regulating the various mediators of NLRP3 inflammasome pathway including TLR4, NF-kB, NLRP3, and caspase 1. We also discussed the importance of NLRP3 inflammasome pathway-related ncRNAs as a diagnostic biomarker in atherosclerosis and current therapeutics in the modulation of NLRP3 inflammasome in atherosclerosis. Finally, we speak about the limitations and future prospects of ncRNAs in regulating inflammatory atherosclerosis via the NLRP3 inflammasome pathway.

Toward automated assessment of mole similarity on dermoscopic images.

Purpose: Current skin cancer detection relies on dermatologists' visual assessments of moles directly or dermoscopically. Our goal is to show that our similarity assessment algorithm on dermoscopic images can perform as well as a dermatologist's assessment. Approach: Given one target mole and two other moles from the same patient, our model determines which mole is more similar to the target mole. Similarity was quantified as the Euclidean distance in a feature space designed to capture mole properties such as size, shape, and color. We tested our model on 18 patients, each of whom had at least five moles, and compared the model assessments of mole similarity with that of three dermatologists. Fleiss' Kappa agreement coefficients and iteration tests were used to evaluate the agreement in similarity assessment among dermatologists and our model. Results: With the selected features of size, entropy (color variation), and cluster prominence (asymmetry), our algorithm's similarity assessments agreed moderately with the similarity assessments of dermatologists. The mean Kappa of 1000 iteration tests was 0.49 ( confidence interval ( CI ) = [ 0.23 , 0.74 ] ) when comparing three dermatologists and our model, which is comparable to the agreement in similarity assessment among the dermatologists themselves (the mean Kappa of 1000 iteration tests for three dermatologists was 0.48, CI = [ 0.19 , 0.77 ] .) By contrast, the mean Kappa was 0.22 ( CI = [ - 0.00 , 0.43 ] ) when comparing the similarity assessments of three dermatologists and random guesses. Conclusions: Our study showed that our image feature-engineering-based algorithm can effectively assess the similarity of moles as dermatologists do. Such a similarity assessment could serve as the foundation for computer-assisted intra-patient evaluation of moles.

Knowledge of Pharmacists about Anti-epileptic Drugs in a Developing Country.

BACKGROUND: Pharmacists play an essential role in educating the epileptic patients about their disease and their medications. Improving the patient's awareness may lead to improve their compliance and decrease drug-drug interaction and ultimately improve their quality of life. OBJECTIVE: This study aimed to assess the pharmacist's knowledge about anti-epileptic drugs in Khartoum State, Sudan. METHODS: We conducted a descriptive cross-sectional study in Khartoum State, Sudan. Proportionate stratified sampling was used to determine the targeted Pharmacies, and all pharmacists who were present in the selected pharmacy at the time of data collection and fulfilled our selection criteria were included in the study. A structure closed-ended questionnaire was used to collect quantitative data from candidates. RESULTS: Majority of participants were female (66.9%), less than 30 years old (66.7%) and have less than 5 years of experience (62.1%). Unfortunately, the majority of the participants (85.3%) had poor knowledge, and only (14.7%) of them had good knowledge. Furthermore, the study revealed that age (p =.030), years of experience (p =.026) and the degree in pharmacy (p = .003) were significantly associated with knowledge level. CONCLUSION: Majority of the pharmacists in Khartoum State have poor knowledge about anti-epileptic drugs. Further research is needed to investigate the actual factors behind this knowledge gap and to propose interventions to improve the pharmacist's knowledge and practice aiming to improve the quality of health care provided to the patients.

Using Nonpolio Enterovirus Detection to Assess the Integrity of Stool Specimens Collected From Acute Flaccid Paralysis Cases in Somalia During 2014-2017.

BACKGROUND: Despite insecurity challenges in Somalia, key indicators for acute flaccid paralysis (AFP) surveillance have met recommended targets. However, recent outbreaks of vaccine-derived polioviruses have raised concerns about possible gaps. We analyzed nonpolio enterovirus (NPEV) and Sabin poliovirus isolation rates to investigate whether comparing these rates can inform about the integrity of stool specimens from inaccessible areas and the likelihood of detecting circulating polioviruses. METHODS: Using logistic regression, we analyzed case-based AFP surveillance data for 1348 cases with onset during 2014-2017. We assessed the adjusted impacts of variables including age, accessibility, and Sabin-like virus isolation on NPEV detection. RESULTS: NPEVs were more likely to be isolated from AFP case patients reported from inaccessible areas than accessible areas (23% vs 15%; P = .01). In a multivariable model, inaccessibility and detection of Sabin-like virus were positively associated with NPEV detection (adjusted odds ratio [AOR], 1.75; 95% confidence interval [CI], 1.14-2.65; and AOR, 1.79; 95% CI, 1.07-2.90; respectively), while being aged ≥5 years was negatively associated (AOR, 0.42; 95% CI, 0.20-0.85). CONCLUSIONS: Rates of NPEV and Sabin poliovirus detection in inaccessible areas suggest that the integrity of fecal specimens tested for AFP surveillance in Somalia can generate useful AFP data, but uncertainties remain about surveillance system quality.

The burden of malaria in Sudan: incidence, mortality and disability--adjusted life--years.

BACKGROUND: Estimating the burden of malaria in Sudan is important for evidence-based planning of malaria control. Estimates of malaria burden in terms of DALYs (Disability Adjusted Life Years) were not developed locally. This study synthesized information from different sources to calculate malaria incidence, mortality and DALYs lost in Sudan in 2002. METHODS: A search for local studies and reports providing epidemiological data on malaria in Sudan was conducted. Preliminary estimates of incidence rate, case fatality rate and mortality rate were developed from the data found. The preliminary estimates were processed in the disease modelling computer software, DisMod II, to produce internally consistent mortality and incidence rates, which were used to calculate DALYs lost due to malaria. RESULTS: Malaria incidence in Sudan was estimated to be about 9 million episodes in 2002 and the number of deaths due to malaria was about 44,000. 2,877,000 DALYs were lost in Sudan in 2002 due to malaria mortality, episodes, anaemia and neurological sequelae. Children under five years of age had the highest burden. Males had the highest incidence and mortality, but females lost more DALYs. CONCLUSION: Formal health system data underestimated malaria burden. The burden estimates can be useful in informing decision making, although uncertainty around them needs to be quantified. Epidemiological research is needed to fill data gaps and update the estimates.