Identifying X (Formerly Twitter) Posts Relevant to Dementia and COVID-19: Machine Learning Approach.

BACKGROUND: During the pandemic, patients with dementia were identified as a vulnerable population. X (formerly Twitter) became an important source of information for people seeking updates on COVID-19, and, therefore, identifying posts (formerly tweets) relevant to dementia can be an important support for patients with dementia and their caregivers. However, mining and coding relevant posts can be daunting due to the sheer volume and high percentage of irrelevant posts. OBJECTIVE: The objective of this study was to automate the identification of posts relevant to dementia and COVID-19 using natural language processing and machine learning (ML) algorithms. METHODS: We used a combination of natural language processing and ML algorithms with manually annotated posts to identify posts relevant to dementia and COVID-19. We used 3 data sets containing more than 100,000 posts and assessed the capability of various algorithms in correctly identifying relevant posts. RESULTS: Our results showed that (pretrained) transfer learning algorithms outperformed traditional ML algorithms in identifying posts relevant to dementia and COVID-19. Among the algorithms tested, the transfer learning algorithm A Lite Bidirectional Encoder Representations from Transformers (ALBERT) achieved an accuracy of 82.92% and an area under the curve of 83.53%. ALBERT substantially outperformed the other algorithms tested, further emphasizing the superior performance of transfer learning algorithms in the classification of posts. CONCLUSIONS: Transfer learning algorithms such as ALBERT are highly effective in identifying topic-specific posts, even when trained with limited or adjacent data, highlighting their superiority over other ML algorithms and applicability to other studies involving analysis of social media posts. Such an automated approach reduces the workload of manual coding of posts and facilitates their analysis for researchers and policy makers to support patients with dementia and their caregivers and other vulnerable populations.

In Situ Nanoencapsulation of Curcumin in Soy Protein Isolate Amyloid-like Aggregates for Enhanced Wound Healing.

The importance of amyloid nanofibrils made from food proteins is rising in diverse fields, such as biomedicine and food science. These protein nanofibrils (PNFs) serve as versatile and sustainable building blocks for biomaterials, characterized by their high ß-sheet content and an ordered hydrogen bond network. These properties offer both stability and flexibility, along with an extreme aspect ratio and reactive functional groups. Plant-derived amyloid nanofibrils, such as soy protein isolate (SPI) PNFs, are increasingly favored due to their affordability and sustainability compared with animal proteins. This study aimed to explore the formation and application of SPI amyloid-like aggregates (SPIA) and their nanoencapsulation of curcumin (Cur) for biomedical purposes, particularly in wound healing. Under specific conditions of low pH and high temperature, SPIA formed, exhibited an amyloid nature, and successfully encapsulated Cur, thereby enhancing its stability and availability. Spectroscopic and microscopic analyses confirmed structural changes in SPIA upon the incorporation of Cur and the fabrication of SPIA@Cur. The obtained results indicate that in the presence of Cur, SPIA forms faster, attributed to accelerated SPI denaturation, an increased nucleation rate, and enhanced self-assembly facilitated by Cur's hydrophobic interactions and π-π stacking with SPI peptides. In vitro studies demonstrated the biocompatibility, biodegradability, and antioxidant properties of SPIA@Cur along with controlled release behavior. In vivo experiments in male Wistar rats revealed that both SPIA and SPIA@Cur significantly accelerate wound closure compared with untreated wounds, with SPIA@Cur showing slightly better efficacy. The histological analysis supported enhanced wound healing, indicating the potential of SPIA@Cur for biomedical applications.

Current and future immunotherapeutic approaches in pancreatic cancer treatment.

Pancreatic cancer is a major cause of cancer-related death, but despondently, the outlook and prognosis for this resistant type of tumor have remained grim for a long time. Currently, it is extremely challenging to prevent or detect it early enough for effective treatment because patients rarely exhibit symptoms and there are no reliable indicators for detection. Most patients have advanced or spreading cancer that is difficult to treat, and treatments like chemotherapy and radiotherapy can only slightly prolong their life by a few months. Immunotherapy has revolutionized the treatment of pancreatic cancer, yet its effectiveness is limited by the tumor's immunosuppressive and hard-to-reach microenvironment. First, this article explains the immunosuppressive microenvironment of pancreatic cancer and highlights a wide range of immunotherapy options, including therapies involving oncolytic viruses, modified T cells (T-cell receptor [TCR]-engineered and chimeric antigen receptor [CAR] T-cell therapy), CAR natural killer cell therapy, cytokine-induced killer cells, immune checkpoint inhibitors, immunomodulators, cancer vaccines, and strategies targeting myeloid cells in the context of contemporary knowledge and future trends. Lastly, it discusses the main challenges ahead of pancreatic cancer immunotherapy.

Narrow-linewidth Fano microcavities with resonant subwavelength grating mirror.

We report on the theoretical and experimental investigations of optical microcavities consisting in the plane-plane arrangement of a broadband high-reflectivity mirror and a suspended one-dimensional grating mirror possessing a high-quality factor Fano resonance. By varying the length of these cavities from the millimeter to the few-micron range, we observe at short lengths the reduction of the spectral linewidth predicted to occur for such a Fano cavity as compared to a conventional broadband mirror cavity with the same length and internal losses. Such narrow linewidth and small modevolume microcavities with high-mechanical quality ultrathin mirrors will be attractive for a wide range of applications within optomechanics and sensing.

TAK-242 (Resatorvid) inhibits proinflammatory cytokine production through the inhibition of NF-κB signaling pathway in fibroblast-like synoviocytes in osteoarthritis patients.

BACKGROUND: Fibroblast-like synoviocytes (FLSs) are involved in osteoarthritis (OA) pathogenesis through pro-inflammatory cytokine production. TAK-242, a TLR4 blocker, has been found to have a significant impact on the gene expression profile of pro-inflammatory cytokines such as IL1-ß, IL-6, TNF-α, and TLR4, as well as the phosphorylation of Ikßα, a regulator of the NF-κB signaling pathway, in OA-FLSs. This study aims to investigate this effect because TLR4 plays a crucial role in inflammatory responses. MATERIALS AND METHODS: Ten OA patients' synovial tissues were acquired, and isolated FLSs were cultured in DMEM in order to assess the effectiveness of TAK-242. The treated FLSs with TAK-242 and Lipopolysaccharides (LPS) were analyzed for the mRNA expression level of IL1-ß, IL-6, TNF-α, and TLR4 levels by Real-Time PCR. Besides, we used western blot to assess the protein levels of Ikßα and pIkßα. RESULTS: The results represented that TAK-242 effectively suppressed the gene expression of inflammatory cytokines IL1-ß, IL-6, TNF-α, and TLR4 which were overexpressed upon LPS treatment. Additionally, TAK-242 inhibited the phosphorylation of Ikßα which was increased by LPS treatment. CONCLUSION: According to our results, TAK-242 shows promising inhibitory effects on TLR4-mediated inflammatory responses in OA-FLSs by targeting the NF-κB pathway. TLR4 inhibitors, such as TAK-242, may be useful therapeutic agents to reduce inflammation and its associated complications in OA patients, since traditional and biological treatments may not be adequate for all of them.

Clinical characteristics, outcome, and factors associated with mortality of pulmonary mucormycosis: a retrospective single-center study from Pakistan.

Introduction and objective: Pulmonary mucormycosis is a rare but rapidly progressive fatal disease. Limited data exist on the outcomes and factors associated with poor prognosis of pulmonary mucormycosis. The objective of this study was to evaluate clinical characteristics, factors associated with mortality, and outcomes of pulmonary mucormycosis at a tertiary care hospital in Pakistan. Methods: This was a retrospective observational study conducted at a tertiary care hospital in Karachi, Pakistan. Medical records of hospitalized patients diagnosed with proven or probable pulmonary mucormycosis between January 2018 and December 2022 were reviewed. Univariate and regression analyses were performed to identify factors associated with mortality. Results: Fifty-three pulmonary mucormycosis patients (69.8% male) were included, with mean age of 51.19 ± 21.65 years. Diabetes mellitus was the most common comorbidity [n = 26 (49.1%)]. Chronic lung diseases were present in [n = 5 (9.4%)], and [n = 16 (30.2%)] had concurrent coronavirus disease 2019 (COVID-19) pneumonia. The predominant isolated Mucorales were Rhizopus [n = 32 (60.3%)] and Mucor species [n = 9 (17%)]. Main radiological findings included consolidation [n = 39 (73.6%)] and nodules [n = 14 (26.4%)]. Amphotericin B deoxycholate was prescribed in [n = 38 (71.7%)], and [n = 14 (26.4%)] of patients received combined medical and surgical treatment. The median [interquartile range (IQR)] hospital stay was 15.0 (10.0-21.5) days. Intensive care unit (ICU) care was required in [n = 30 (56.6%)] patients, with 26 (49.1%) needing mechanical ventilation. Overall mortality was seen in 29 (54.7%) patients. Significantly higher mortality was found among patients requiring mechanical ventilation 20/29 (69%, p = 0.002). Immunosuppression (p = 0.042), thrombocytopenia (p = 0.004), and mechanical ventilation (p = 0.018) were identified as risk factors for mortality on multivariable analysis. Conclusion: This study provides essential insights into the clinical characteristics, outcomes, and mortality factors associated with pulmonary mucormycosis. The mortality rate was high (54.7%), particularly in patients with immunosuppression, thrombocytopenia, and those who required mechanical ventilation.

Prevalence of Complementary and Alternative Medicine Use and Its Associated Factors among Iranian Diabetic Patients: A Cross-Sectional Study.

Objective: This cross-sectional study aimed to assess the prevalence of complementary and alternative medicine (CAM) use and its associated factors among diabetic patients in Fasa, a city in southern Iran. Methods: Data were collected from diabetic patients who visited the endocrinology clinics at Fasa University of Medical Sciences. A structured questionnaire was administered to gather information on CAM use, including the types of CAM modalities used, and reasons for use. The patient's demographic and clinical characteristics, such as age, gender, duration of diabetes, glycosylated hemoglobin (HbA1c) levels, and quality of life (QoL) were also recorded. Descriptive statistics were used to determine the prevalence of CAM use, while logistic regression analysis was employed to identify factors associated with CAM use. Results: A total of 376 diabetic patients participated in the study, with more than 89% reporting CAM use within the past year. Herbal preparations were the most commonly used type of CAM, with a prevalence rate of 99.4%. Factors associated with CAM use included patients' psychological health, attitude towards the safety of CAM, belief in the synergistic effects of combining routine medications with CAM, and previous positive experiences with CAM. Conclusion: The high prevalence of CAM use highlights the importance of considering it in diabetes management and the need for healthcare professionals' engagement in open discussions with patients about their CAM practices. Understanding the factors influencing CAM use can inform healthcare providers and policymakers in developing appropriate strategies for integrating CAM approaches into conventional diabetes care.

The association between healthy eating index-2015 with anthropometric, cardiometabolic and hepatic indices among patients with non-alcoholic fatty liver disease.

BACKGROUND: Obesity, cardiovascular diseases, and metabolic disorders are common problems among participants with non-alcoholic fatty liver disease (NAFLD). However, the association between these problems and the healthy eating index-2015 (HEI-2015) remains unknown. Although the HEI-2015 originated from American dietary guidelines, its comprehensive evaluation of diet quality provides valuable insights for various populations, including Iranians. Therefore, the objective of this study was to investigate the association between anthropometric, hepatic, and cardio-metabolic indices with HEI-2015 scores in participants with NAFLD. METHODS: We conducted a cross-sectional analysis of data from the Hoveyzeh Cohort Study, which included adults aged 35 to 70 years between 2016 and 2018. A total of 664 participant with NAFLD (452 females and 212 males) were included in the analysis. The HEI-2015 was assessed using the Food Frequency Questionnaire (FFQ). Various indices, including the body shape index (ABSI), atherogenic index of plasma (AIP), visceral adiposity index (VAI), lipid accumulation product (LAP), cardiometabolic index (CMI), lipoprotein combine index (LCI), AST/ALT ratio, ALD/NAFLD index, and hepatic steatosis index (HSI), were calculated. RESULTS: No significant differences were observed in anthropometric, cardio-metabolic, and hepatic indices across the quartiles of HEI-2015. However, among participants with NAFLD, men had significantly higher AIP and LCI levels, while women had significantly higher BMI, ABSI, VAI, LAP, and CMI levels. Additionally, women with NAFLD exhibited higher AST/ALT and HSI levels but lower ALD/NAFLD levels compared to men with NAFLD. Linear regression analysis among men with NAFLD revealed a significant negative correlation between HEI-2015 score and HSI in both the unadjusted model (ß=-0.131, SE = 0.058, p = 0.024) and the adjusted model for energy intake (ß=-0.129, SE = 0.058, p = 0.028). CONCLUSION: The present study demonstrated a correlation between lower HEI-2015 scores and an increased risk of steatosis in men with NAFLD. Moreover, our findings highlighted gender-related differences in NAFLD and cardio-metabolic disorders.

Prediction of the First-Pass Metabolism of a Drug After Oral Intake Based on Structural Parameters and Physicochemical Properties.

BACKGROUND AND OBJECTIVE: The oral first-pass metabolism is a crucial factor that plays a key role in a drug's pharmacokinetic profile. Prediction of the oral first-pass metabolism based on chemical structural parameters can be useful in the drug-design process. Developing an orally administered drug with an acceptable pharmacokinetic profile is necessary to reduce the cost and time associated with evaluating the extent of the first-pass metabolism of a candidate compound in preclinical studies. The aim of this study is to estimate the first-pass metabolism of an orally administered drug. METHODS: A set of compounds with reported first-pass metabolism data were collected. Moreover, human intestinal absorption percentage and oral bioavailability data were extracted from the literature to propose a classification system that split the drugs up based on their first-pass metabolism extents. Various structural parameters were calculated for each compound. The relations of the structural and physicochemical values of each compound to the class the compound belongs to were obtained using logistic regression. RESULTS: Initial analysis showed that compounds with logD7.4 > 1 or a rugosity factor of > 1.5 are more likely to have high first-pass metabolism. Four different models that can predict the oral first-pass metabolism with acceptable error were introduced. The overall accuracies of the models were in the range of 72% (for models with simple descriptors) to 78% (for models with complex descriptors). Although the models with simple descriptors have lower accuracies compared to complex models, they are more interpretable and easier for researchers to utilize. CONCLUSION: A novel classification of drugs based on the extent of the oral first-pass metabolism was introduced, and mechanistic models were developed to assign candidate compounds to the appropriate proposed classes.

Genome-wide association study of copy number variations with shank traits in a F2 crossbred chicken population.

Copy number variations (CNVs) are large-scale changes in the DNA sequence that can affect the genetic structure and phenotype of an organism. The purpose of this study was to investigate the existing CNVs and their associations with the shank diameter (ShD) and shank length (ShL) traits using data from an F2 crossbred chicken population. To carry out the study, 312 chickens were genotyped using the Illumina 60k SNP Beadchip. The shank traits of the birds were measured from day 1 to 12 weeks of age. penncnv and cnvruler tools were used to find copy numbers and regions with copy number changes (CNVR), respectively. The CNVRanger package was used to perform a genome-wide association study between shank traits and CNVs. Gene ontology research in CNVRs was carried out using the david database. In this investigation, 966 CNVs and 606 regions with copy number changes were discovered. The copy number states and variations were randomly distributed along the length of the autosomal chromosomes. Weeks 1-4, 9 and 12 of growth revealed a significant association of copy number variations with shank traits, false discovery rate (FDR-corrected p-value < 0.01), and the majority of CNVs that were statistically significant were found on chromosomes 1-3. These CNV segments are nearby genes such as KCNJ12, FGF6 and MYF5, which are fundamental to growth and development. In addition, gene set analyses revealed terms related to muscle physiology, regulation of cellular processes and potassium channels.

The Role of Efflux Pumps transporter in Multi-drug Resistant Tuberculosis: Mycobacterial memberane protein(MmpL5).

BACKGROUND: The overexpression of efflux pumps (Eps) was reported to contribute to multidrug resistant tuberculosis (MDR-TB). Increases in Eps that expel structurally unrelated drugs contribute to reduced susceptibility by decreasing the intracellular concentration of antibiotics. In the present study, an association of mycobacterial membrane protein (MmpS5-MmpL5) Ep and its gene regulator (Rv0678) was investigated in MDR-tuberculosis isolates. METHODS: MTB strains were isolated from patients at two different intervals, i.e., once when they had persistent symptoms despite 3-15 ≥ months of treatment and once when they had started new combination therapy ≥2-3 months. Sputum specimens were subjected to Xpert MTB/rifampicin test and then further susceptibility testing using proportional method and multiplex polymerase chain reaction (PCR) were performed on them. The isolates were characterized using both 16S-23S RNA and hsp65 genes spacer (PCR-restriction fragment length polymorphism). Whole-genome sequencing (WGS) was investigated on two isolates from culture-positive specimen per patient. The protein structure was simulated using the SWISS-MODEL. The input format used for this web server was FASTA (amino acid sequence). Protein structure was also analysis using Ramachandran plot. RESULTS: WGS documented deletion, insertion, and substitution in transmembrane transport protein MmpL5 (Rv0676) of Eps. Majority of the studied isolates (n = 12; 92.3%) showed a unique deletion mutation at three positions: (a) from amino acid number 771 (isoleucine) to 776 (valine), (b) from amino acid number 785 (valine) to 793 (histidine), and (c) from amino acid number 798 (leucine) to 806 (glycine)." One isolate (7.6%) had no deletion mutation. In all isolates (n = 13; 100%), a large insertion mutation consisting of 94 amino acid was observed "from amino acid number 846 (isoleucine) to amino acid number 939 (leucine)". Thirty-eight substitutions in Rv0676 were detected, of which 92.3% were identical in the studied isolates. WGS of mycobacterial membrane proteins (MmpS5; Rv0677) and its gene regulator (Rv0678) documented no deletion, insertion, and substitution. No differences were observed between MmpS5-MmpL5 and its gene regulator in isolates that were collected at different intervals. CONCLUSIONS: Significant genetic mutation like insertion, deletion, and substitution within transmembrane transport protein MmpL5 (Rv0676) can change the functional balance of Eps and cause a reduction in drug susceptibility. This is the first report documenting a unique amino acid mutation (insertion and deletion ≥4-94) in Rv0676 among drug-resistant MTB. We suggest the changes in Mmpl5 (Rv0676) might occurred due to in-vivo sub-therapeutic drug stress within the host cell. Changes in MmpL5 are stable and detected through subsequent culture-positive specimens.

A qualitative study exploring approaches, barriers, and facilitators of the HIV partner notification program in Kerman, Iran.

BACKGROUND: HIV partner notification services can help people living with HIV (PLHIV) to identify, locate, and inform their sexual and injecting partners who are exposed to HIV and refer them for proper and timely counseling and testing. To what extent these services were used by PLHIV and what are the related barriers and facilitators in southeast Iran are not known. So, this study aimed to explore HIV notification and its barriers and facilitators among PLHIV in Iran. METHODS: In this qualitative study, the number of 23 participants were recruited from November 2022 to February 2023 including PLHIV (N = 12), sexual partners of PLHIV (N = 5), and staff members (N = 6) of a Voluntary Counseling and Testing (VCT) center in Kerman located in the southeast of Iran. Our data collection included purposive sampling to increase variation. The content analysis was conducted using the Graneheim and Lundman approach. The analysis yielded 221 (out of 322) related codes related to HIV notification, its barriers, and its facilitators. These codes were further categorized into one main category with three categories and nine sub-categories. RESULTS: The main category was HIV notification approaches, HIV notification barriers, and facilitators. HIV notification approaches were notification through clear, and direct conversation, notification through gradual preparation and reassurance, notification due to being with PLHIV, notification through suspicious talking of the physician, and notification due to the behavior of others. Also, the barriers were classified into individual, social, and environmental, and healthcare system barriers and the facilitators were at PLHIV, healthcare staff, and community levels. Stigma was a barrier mentioned by most participants. Also, the main facilitator of HIV notification was social support, especially from the family side. CONCLUSIONS: The findings highlighted the multidimensionality of HIV notification emphasizing the importance of tailored support and education to enhance the notification process for PLHIV and their networks. Also, our results show that despite all the efforts to reduce stigma and discrimination in recent years, stigma still exists as a main obstacle to disclosing HIV status and other barriers are the product of stigma. It seems that all programs should be directed towards destigmatization.

Vitamin D and reproductive disorders: a comprehensive review with a focus on endometriosis.

Vitamin D is a fat-soluble steroid hormone that was initially known only for regulating calcium and phosphorus levels and maintaining bone health. However, it was later discovered that many organs express vitamin D metabolizing enzymes and have a ligand for vitamin D, which regulates the expression of an extensive assortment of genes. As a result, vitamin D is indispensable for the proper function of organs, and its deficiency is believed to be a critical factor in symptoms and disorders such as cardiovascular diseases, autoimmune diseases, and cancers. The significance of vitamin D in reproductive tissues was recognized later, and studies have revealed its crucial role in male and female fertility, as well as proper reproductive function during pregnancy. Vitamin D deficiency has been identified as a risk factor for infertility, gonadal cancers, pregnancy complications, polycystic ovary syndrome, and endometriosis. However, data investigating the association between vitamin D levels and reproductive disorders, including endometriosis, have encountered inconsistencies. Therefore, the present study aims to review existing research on the effect of vitamin D on proper reproductive function, and the role of deficiency in reproductive diseases and specifically focuses on endometriosis.

Bioelectrocatalytic Activity of One-Dimensional Porous Pt Nanoribbons for Efficient Inhibition of Tumor Growth and Metastasis.

Designing and synthesizing one-dimensional porous Pt nanocrystals with unique optical, electrocatalytic, and theranostic properties are gaining lots of attention, especially to overcome the challenges of tumor recurrence and resistance to platinum-based chemotherapy. Herein, we represented an interesting report of a one-step and facile strategy for synthesizing multifunctional one-dimensional (1D) porous Pt nanoribbons (PtNRBs) with highly efficient therapeutic effects on cancer cells based on inherent electrocatalytic activity. The critical point in the formation of luminescent porous PtNRBs was the use of human hemoglobin (Hb) as a shape-regulating, stabilizing, and reducing agent with facet-specific domains on which fluorescent platinum nanoclusters at first are aggregated by aggregation-induced emission phenomena (AIE) and then crystallized into contact and penetration twins, as intermediate products, followed by shaping of the final luminescent porous ribbon nanomaterials, owing to oriented attachment association via the Ostwald ripening mechanism. From a medical point of view, the key strategy for effective cancer therapy occured via using low-dosage ethanol in the presence of electroactive porous PtNRBs based on intracellular ethanol oxidation-mediated reactive oxygen species (ROS) generation. The role of heme groups of Hb, as electrocatalytically active centers, was successfully demonstrated in both kinetically controlled anisotropic growth of NRBs for slowing down the reduction of Pt(II) followed by oligomerization of Pt(II)-Hb complexes via platinophilic interactions as well as electrocatalytic ethanol oxidation for therapy. Interestingly, hyaluronic acid-targeted (HA) Hb-PtNRB in the presence of low-dose ethanol caused extraordinary arrest of tumor growth and metastasis with no recurrence even after the treatment course stopped, which caused elongation of tumor-bearing mice survival. HA/Hb-PtNRB was completely biocompatible and exhibited high tumor-targeting efficacy for fluorescent imaging of breast tumors. Therefore, the synergistic electrocatalytic activity of PtNRBs is presented as an efficient and safe cancer theranostic method for the first time.

Comparative Evaluation of Levamisole and Broccoli in Mitigating Testicular Oxidative Stress and Apoptotic Alterations Caused by Cadmium and Lead Exposure in Rats.

Considering the significance of heavy metals in infertility and their reduction through natural and synthetic compounds, a comparative study of broccoli and levamisole in cadmium and lead poisoning was conducted. Male Wistar rats (48 in total) were divided into 8 groups. Control, cadmium, lead, levamisole, and broccoli were administered individually to groups 1-5, while groups 6-8 received combinations. Various measurements were taken, including final weight, testicular weight, and the GSI coefficient. Sperm parameters, spermatogenesis cell count, oxidative stress biomarkers, and apoptosis indices were assessed using ELISA kits and methods in testicular tissue. The results indicated that the GSI coefficient was lowest in group 2 and highest in group 4, showing a significant difference (P < 0.001). Sperm concentration peaked in group 1 and broccoli-treated ones, while motility was highest in group 5. Testicular cell counts and Johnson score were highest in groups 1 and 2, and lowest in cadmium-exposed groups. These differences were statistically significant at P < 0.01. Enzyme activities related to oxidative stress varied. Group 2 exhibited the highest catalase (CAT) and superoxide dismutase (SOD) activities, while glutathione peroxidase (GPx) levels peaked in groups 1, 4, and 5. Malondialdehyde (MDA) concentrations were significantly reduced in the group 5 (P < 0.05). Apoptosis indices revealed that broccoli had the highest Bcl-2 levels and lowest Bax/Bcl-2 ratio, indicating its anti-apoptotic effect. Group 4 showed less efficacy compared to broccoli in protecting fertility indices. In conclusion, cadmium and lead significantly impact male fertility, while broccoli extract demonstrates promising efficacy in mitigating damage when compared to levamisole. This underscores its antioxidant and anti-apoptotic properties.

Protective effect of melatonin against methamphetamine-induced attention deficits through miR-181/SIRT1 axis in the prefrontal cortex.

INTRODUCTION: Methamphetamine (METH) is an addictive psychostimulant with deleterious effects on the central nervous system. Chronic use of METH in high doses impairs cognition, attention and executive functions, but the underlying mechanisms are still unclear. Sirtuin 1 (SIRT1) is a post-translational regulator that is downregulated following METH neurotoxicity. Melatonin is a neuroprotective hormone that enhances mitochondrial metabolism. Here, we evaluated the effect of melatonin on METH-induced attention deficits disorder and the involvement of the miR-181/SIRT1 axis in melatonin neuroprotection. METHODS AND RESULTS: METH at a dose of 5 mg/kg was injected for 21 consecutive days. The animals were assigned to receive either melatonin or the vehicle after METH injections. Attention levels were evaluated with abject-based attention test. In the prefrontal cortex, the expression levels of miR-181a-5p, SIRT1, p53 and CCAR2, as well as the mtDNA copy numbers were evaluated using qRT-PCR and western blotting. The outcomes revealed that melatonin treatment following METH injections improved METH-induced attention deficits. METH toxicity can be associated with changes in the miR-181/SIRT1 axis, elevated levels of p53 and COXII, and decreased levels of mtDNA in the prefrontal cortex of adult rats. Interestingly, administration of melatonin can improve the expression of these molecules and reduces the toxic effects of METH. CONCLUSION: Melatonin ameliorated the neurotoxicity of METH in the prefrontal cortex and the miR-181/SIRT1 axis is involve in the protective effects of melatonin. However, melatonin can be potentially administrated to improve attention impairment in METH use disorders.

Synthesis and characterization of amino-functionalized guar gum based polyurea: Preparation of iodine complexes, structural investigation and release studies.

Biobased materials are expanding dramatically in various industrial applications due to their unique intrinsic properties. In this study, various chemical functionalization procedures were used to synthesize guar gum, a naturally occurring polysaccharide-based polyurea, and its iodine complexes. Firstly, guar gum was subjected to tosylation reaction using p-toluene sulphonyl chloride to introduce tosyl moieties in the polymer chain with the degree of substitution (DS) ranging between 0.16 and 1.54. Sample having the highest degree of tosyl moiety was further reacted with tris(2-aminoethyl) amine to produce 6-deoxy-6-tris(2-aminoethyl) amine derivative via nucleophilic substitution reaction to impart amino functional groups. The degree of substitution in 6-deoxy-6-tris(2-aminoethyl) amine derivative was found to be 0.59. 6-deoxy-6-tris(2-aminoethyl) amine derivative was reacted with different diisocyanates (Toluene-2,4-diisocyanate (TDI), 1,6-diisocyanatohexane (HMDI)) to produce guar gum based polyurea. Iodine complexes of the resulting polyurea were prepared by reacting with different iodinating agents. Different chemical reactions, formation of polyurea and its iodine complexes were thoroughly analyzed by different analytical techniques such as FT-IR, NMR, elemental analysis, XRD, UV-Vis spectroscopy, and a reaction scheme has been proposed. Morphological and rheological characteristics were analyzed by SEM and viscosity measurement. Thermal analysis was carried out by TGA and DSC studies. Finally, by examining the complex's UV-Vis spectra, the iodine release characteristics from polyurea­iodine complexes were investigated.

A critical review of the recent concept of regulatory performance of DNA Methylations, and DNA methyltransferase enzymes alongside the induction of immune microenvironment elements in recurrent pregnancy loss.

Recurrent pregnancy Loss (RPL)is a frequent and upsetting condition. Besides the prevalent cause of RPL including chromosomal defects in the embryo,the effect of translational elements like alterations of epigenetics are of great importance. The emergence of epigenetics has offered a fresh outlook on the causes and treatment of RPL by focusing on the examination of DNA methylation. RPL may arise as a result of aberrant DNA methylation of imprinted genes, placenta-specific genes, immune-related genes, and sperm DNA, which may have a direct or indirect impact on embryo implantation, growth, and development. Moreover, the distinct immunological tolerogenic milieu established at the interface between the mother and fetus plays a crucial role in sustaining pregnancy. Given this, there has been a great deal of interest in the regulation of DNA methylation and alterations in the cellular components of the maternal-fetal immunological milieu. The research on DNA methylation's role in RPL incidence and the control of the mother-fetal immunological milieu is summed up in this review.

Association Between Ki-67 Proliferative Index and Oncotype-Dx Recurrence Score in Hormone Receptor-Positive, HER2-Negative Early Breast Cancers. A Systematic Review of the Literature.

Background: Oncotype-Dx (ODx) is a 21-gene assay used as a prognostic and predictive tool for hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative, node-negative, or 1 to 3 lymph node-positive early breast cancers (EBCs). The cost of the test, which is not available in low-middle income countries (LMICs), is not within the means of most individuals. The Ki-67 index is a marker of tumor proliferation that is cost-effective and easily performed and has been substituted in many cases to obtain prognostic information. Objective: We aimed to identify the correlation between the ODx recurrence score (RS) and the Ki-67 index in HR-positive EBCs and to determine whether Ki-67, like the ODx, can help facilitate clinical decision-making. Design: Systematic review correlating Ki-67 index and ODx in HR-positive and HER2-negative EBCs as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data sources and methods: We searched different databases between January 2010 and May 2023 and included retrospective/prospective cohorts, clinical trials, case-control, and cross-sectional studies involving HR-positive and HER2-negative EBCs correlating the Ki-67 index and ODx RS categories. Results: Of the 18 studies included, 16 indicated a positive or weakly positive correlation between ODx and the Ki-67 index. The combined P value of the included studies is <0.05 (P = .000), which shows a statistical significance between the 2. Our review also discusses the potential of machine learning and artificial intelligence (AI) in Ki-67 assessment, offering a cost-effective and reproducible alternative. Conclusion: Even although there are limitations, studies indicate a favorable association between ODx and the Ki-67 index in specific situations. This implies that Ki-67 can offer important predictive details, especially regarding the likelihood of relapse in HR-positive EBC. This is particularly significant in LMICs where financial constraints often hinder the availability of costly diagnostic tests.

Comparing Ki-67 and Oncotype-Dx Tests for Predicting Early Breast Cancer Outcomes: A Comprehensive Review The study explored the correlation between the expensive Oncotype-Dx (ODx) test and the more affordable Ki-67 index in predicting outcomes for certain breast cancers. Results from 16 out of 18 studies indicated a significant link between the 2 tests, suggesting Ki-67 could be a cost-effective alternative, especially in low- to middle-income countries.