Cytoplasmic Expression of p16 Is Associated with Carcinoma Breast: It Is Not an Artifact.

Background & Objective: p16 has different roles in the nuclear and cytoplasmic locations. The nuclear localization of the p16 protein explains its role in cell cycle regulation. Cytoplasmic expression was considered an artifact in the initial years, but there is evidence to prove that cytoplasmic localization is real and that p16 has different roles in the nuclear and cytoplasmic locations. We aimed to study the immunoexpression of p16 protein in the nuclear and cytoplasmic locations of the epithelial and stromal compartments of fibroadenoma, invasive breast carcinoma, and a select number of phyllodes tumors. Methods: The study included a total of 107 patients, comprising 51 cases of invasive breast carcinoma, 51 cases of fibroadenoma, 4 cases of benign phyllodes tumors, and 1 case of lobular carcinoma in situ (LCIS). The p16 immunohistochemistry was evaluated for nuclear and cytoplasmic localization in the epithelial and stromal compartments of the tumors. Results: Of the 51 fibroadenoma cases, 23 showed strong nuclear p16 epithelial expression, but no case showed cytoplasmic expression. In 19/51 cases, stromal cells also showed strong p16 nuclear expression. Moderate stromal p16 expression was observed in 3 out of 4 cases of benign phyllodes. Out of the 51 cases of invasive carcinoma, 31 showed moderate to strong nuclear p16 immunopositivity, while 27 cases exhibited cytoplasmic p16 expression. We found a statistically significant correlation between moderate to strong nuclear p16 immunoexpression and the molecular subtype of breast carcinoma. Conclusion: The cytoplasmic localization of p16 immunohistochemistry is not seen in epithelial components of fibroadenoma, while it is seen frequently in breast carcinoma. Nuclear p16 expression has a statistically significant correlation with molecular subtypes of breast carcinoma.

Systems modeling of oncogenic G-protein and GPCR signaling reveals unexpected differences in downstream pathway activation.

Mathematical models of biochemical reaction networks are an important and emerging tool for the study of cell signaling networks involved in disease processes. One promising potential application of such mathematical models is the study of how disease-causing mutations promote the signaling phenotype that contributes to the disease. It is commonly assumed that one must have a thorough characterization of the network readily available for mathematical modeling to be useful, but we hypothesized that mathematical modeling could be useful when there is incomplete knowledge and that it could be a tool for discovery that opens new areas for further exploration. In the present study, we first develop a mechanistic mathematical model of a G-protein coupled receptor signaling network that is mutated in almost all cases of uveal melanoma and use model-driven explorations to uncover and explore multiple new areas for investigating this disease. Modeling the two major, mutually-exclusive, oncogenic mutations (Gαq/11 and CysLT2R) revealed the potential for previously unknown qualitative differences between seemingly interchangeable disease-promoting mutations, and our experiments confirmed oncogenic CysLT2R was impaired at activating the FAK/YAP/TAZ pathway relative to Gαq/11. This led us to hypothesize that CYSLTR2 mutations in UM must co-occur with other mutations to activate FAK/YAP/TAZ signaling, and our bioinformatic analysis uncovers a role for co-occurring mutations involving the plexin/semaphorin pathway, which has been shown capable of activating this pathway. Overall, this work highlights the power of mechanism-based computational systems biology as a discovery tool that can leverage available information to open new research areas.

Silver and Copper Nanoparticle-Loaded Self-Assembled Pseudo-Peptide Thiourea-Based Organic-Inorganic Hybrid Gel with Antibacterial and Superhydrophobic Properties for Antifouling Surfaces.

The escalating threat of antimicrobial resistance has become a global health crisis. Therefore, there is a rising momentum in developing biomaterials with self-sanitizing capabilities and inherent antibacterial properties. Despite their promising antimicrobial properties, metal nanoparticles (MNPs) have several disadvantages, including increased toxicity as the particle size decreases, leading to oxidative stress and DNA damage that need consideration. One solution is surface functionalization with biocompatible organic ligands, which can improve nanoparticle dispersibility, reduce aggregation, and enable targeted delivery to microbial cells. The existing research predominantly concentrates on the advancement of peptide-based hydrogels for coating materials to prevent bacterial infection, with limited exploration of developing surface coatings using organogels. Herein, we have synthesized organogel-based coatings doped with MNPs that can offer superior hydrophobicity, oleophobicity, and high stability that are not easily achievable with hydrogels. The self-assembled gels displayed distinct morphologies, as revealed by scanning electron microscopy and atomic force microscopy. The cross-linked matrix helps in the controlled and sustained release of MNPs at the site of bacterial infection. The synthesized self-assembled gel@MNPs exhibited excellent antibacterial properties against harmful bacteria such as Escherichia coli and Staphylococcus aureus and reduced bacterial viability up to 95% within 4 h. Cytotoxicity testing against metazoan cells demonstrated that the gels doped with MNPs were nontoxic (IC50 > 100 µM) to mammalian cells. Furthermore, in this study, we coated the organogel@MNPs on cotton fabric and tested it against Gram +ve and Gram -ve bacteria. Additionally, the developed cotton fabric exhibited superhydrophobic properties and developed a barrier that limits the interaction between bacteria and the surface, making it difficult for bacteria to adhere and colonize, which holds potential as a valuable resource for self-cleaning coatings.

Gastrointestinal bleeding in a kidney transplant recipient.

Opportunistic infections are common in transplant recipients, but gastrointestinal bleed is rarely reported to be due to opportunistic fungal infections, and hence could present as a diagnostic challenge. We report a case of disseminated histoplasmosis in a kidney transplant recipient whose initial presentation was acute lower gastrointestinal bleeding with no other symptoms. The colonoscopy showed scattered punchout circular colonic ulcers with biopsy revealing budding yeasts consistent with a diagnosis of histoplasmosis. The patient was successfully treated with a prolonged course of intravenous amphotericin B followed by oral itraconazole.

The impact of hospitalization on mortality in patients with connective tissue disease-associated interstitial lung disease: a medical records review study

Abstract Background Interstitial lung disease (ILD) remains one of the most important causes of morbidity and mortality in patients with Connective Tissue Diseases (CTD). This study evaluated the impact of hospitalization on mortality in an ethnically and racially diverse cohort of CTD-ILD patients. Methods We conducted a medical records review study at Montefiore Medical Center, Bronx, NY. We included 96 patients and collected data on demographic characteristics, reasons for hospitalization, length of stay, immunosuppressant therapy use, and mortality. We stratified our patients into two cohorts: hospitalized and nonhospitalized. The hospitalized cohort was further subdivided into cardiopulmonary and non-cardiopulmonary admissions. Two-sample tests or Wilcoxon's rank sum tests for continuous variables and Chi-square or Fisher's exact tests for categorical variables were used for analyses as deemed appropriate. Results We identified 213 patients with CTD-ILD. Out of them, 96 patients met the study's inclusion criteria. The majority of patients were females (79%), and self-identified as Hispanic (54%) and Black (40%). The most common CTDs were rheumatoid arthritis (RA) (29%), inflammatory myositis (22%), and systemic sclerosis (15%). The majority (76%) of patients required at least one hospitalization. In the non-hospitalized group, no deaths were observed, however we noted significant increase of mortality risk in hospitalized group (p = 0.02). We also observed that prolonged hospital stay (> 7 days) as well as older age and male sex were associated with increased mortality. Conclusion Prolonged (> 7 days) hospital stay and hospitalization for cardiopulmonary causes, as well as older age and male sex were associated with an increased mortality risk in our cohort of CTD-ILD patients.

Reducing the Risk of Acrylamide and Other Processing Contaminant Formation in Wheat Products.

Wheat is a staple crop, consumed worldwide as a major source of starch and protein. Global intake of wheat has increased in recent years, and overall, wheat is considered to be a healthy food, particularly when products are made from whole grains. However, wheat is almost invariably processed before it is consumed, usually via baking and/or toasting, and this can lead to the formation of toxic processing contaminants, including acrylamide, 5-hydroxymethylfurfural (HMF) and polycyclic aromatic hydrocarbons (PAHs). Acrylamide is principally formed from free (soluble, non-protein) asparagine and reducing sugars (glucose, fructose and maltose) within the Maillard reaction and is classified as a Group 2A carcinogen (probably carcinogenic to humans). It also has neurotoxic and developmental effects at high doses. HMF is also generated within the Maillard reaction but can also be formed via the dehydration of fructose or caramelisation. It is frequently found in bread, biscuits, cookies, and cakes. Its molecular structure points to genotoxicity and carcinogenic risks. PAHs are a large class of chemical compounds, many of which are genotoxic, mutagenic, teratogenic and carcinogenic. They are mostly formed during frying, baking and grilling due to incomplete combustion of organic matter. Production of these processing contaminants can be reduced with changes in recipe and processing parameters, along with effective quality control measures. However, in the case of acrylamide and HMF, their formation is also highly dependent on the concentrations of precursors in the grain. Here, we review the synthesis of these contaminants, factors impacting their production and the mitigation measures that can be taken to reduce their formation in wheat products, focusing on the role of genetics and agronomy. We also review the risk management measures adopted by food safety authorities around the world.

Portable Sensor Array for On-Site Detection and Discrimination of Pesticides and Herbicides Using Multivariate Analysis.

Modern agricultural practice relies heavily on pesticides and herbicides to increase crop productivity, and consequently, their residues have a negative impact on the environment and public health. Thus, keeping these issues in account, herein we developed an azodye-based chromogenic sensor array for the detection and discrimination of pesticides and herbicides in food and soil samples, utilizing machine learning approaches such as hierarchical clustering analysis, principal component analysis, linear discriminant analysis (LDA), and partial least square regression (PLSR). The azodye-based sensor array was developed in combination with various metal ions owing to their different photophysical properties, which led to distinct patterns toward various pesticides and herbicides. The obtained distinct patterns were recognized and processed through automated multivariate analysis, which enables the selective and sensitive identification and discrimination of various target analytes. Further, the qualitative and quantitative determination of target analytes were performed using LDA and PLSR; the results obtained show a linear correlation with varied concentrations of target analytes with R2 values from 0.89 to 0.96, the limit of detection from 5.3 to 11.8 ppm with a linear working range from 1 to 30 µM toward analytes under investigation. Further, the developed sensor array was successfully utilized for the discrimination of a binary mixture of pesticide (chlorpyrifos) and herbicide (glyphosate).

An Examination of Coping Strategies that Moderated the Effects of COVID-19-Related Stress on Anxiety Among Older Adults in Aotearoa/NZ.

Objectives: 1. To describe perceived stress and changes in anxiety and coping among older adults between 2018 and 2020. 2. To examine the moderating roles of social support, exercise, alcohol use, and smoking on the relationship between perceived stress and anxiety. Methods: Longitudinal data collected from 3275 participants (M = 68.1 years) as part of the NZ Health, Work, and Retirement study's 2018 and 2020 biennial surveys, were analyzed using hierarchical regression. Results: Older adults perceived COVID-19 as a low-level source of stress. Social support and alcohol use moderated the relationship between perceived mental stress and anxiety. At high-stress levels, only social support exerted a protective effect against the negative impact of stress on anxiety. Discussion: These findings support the general resilience of many older adults and highlight the effectiveness of coping strategies used by those groups who are more likely to be vulnerable to mental stress during a pandemic.

The effect of histone deacetylase inhibitors on the efficiency of the CRISPR/Cas9 system.

The CRISPR/Cas9 technology is a prominent genome-editing tool capable of producing a double-strand break in the genome. However, the modification of hematopoietic stem cells via the homology-directed repair pathway is still inefficient. Therefore, we hypothesize that histone deacetylase inhibitors, such as valproic acid (VPA) and sodium butyrate (NaB), could enhance HDR efficiency by increasing the accessibility of the genome-editing machinery. To address the potential utilization of HDAC inhibitors therapeutically, we began by assessing the effect of VPA and NaB on two cell lines representative of the two hematopoietic stem cell lineages. No statistically significant effect on cell growth or viability was observed at concentrations as high as 5 mM. At a concentration as low as 0.005 mM NaB, an enhancement in CRISPR cutting efficiency was evidenced in both cell lines. This enhancement did not appear to be locus-specific. However, an enhancement in cutting efficiency following VPA treatment does appear to be. HDR efficiency was enhanced greater than two-fold with the use of 0.005 mM VPA. These results are promising and suggest the consideration of treatment with an HDAC inhibitor in CRISPR/Cas9 genome editing protocols.

Design of Silica@Au Hybrid Nanostars for Enhanced SERS and Photothermal Effect.

Core-shell nanostructures of silicon oxide@noble metal have drawn a lot of interest due to their distinctive characteristics and minimal toxicity with remarkable biocompatibility. Due to the unique property of localized surface plasmon resonance (LSPR), plasmonic nanoparticles are being used as surface-enhanced Raman scattering (SERS) based detection of pollutants and photothermal (PT) agents in cancer therapy. Herein, we demonstrate the synthesis of multifunctional silica core - Au nanostars shell (SiO2 @Au NSs) nanostructures using surfactant free aqueous phase method. The SERS performance of the as-synthesized anisotropic core-shell NSs was examined using Rhodamine B (RhB) dye as a Raman probe and resulted in strong enhancement factor of 1.37×106 . Furthermore, SiO2 @Au NSs were also employed for PT killing of breast cancer cells and they exhibited a concentration-dependent increase in the photothermal effect. The SiO2 @Au NSs show remarkable photothermal conversion efficiency of up to 72 % which is unprecedented. As an outcome, our synthesized NIR active SiO2 @Au NSs are of pivotal importance to have their dual applications in SERS enhancement and PT effect.

Hormonal profile of survivors of breast cancer with fatigue: A pilot study.

Background & objectives: One of the most common problems experienced by breast cancer survivors (BCSs) is fatigue. There has been little research about the status of hormones in breast cancer patients as an aetiology of cancer-related fatigue (CRF). Hence, a pilot study was conducted to assess the levels of hormones such as thyroid, cortisol, dehydroepiandrosterone sulphate (DHEAS), oestrogen and progesterone in BCSs with fatigue. Methods: BCSs with complaints of fatigue were assessed using the Brief Fatigue Inventory (BFI) tool and evaluation of the hormone profiles was done in moderate-to-severe fatigued survivors. Data collected were analyzed to look for any association between fatigue and altered hormonal levels. Results: In this study, 56 per cent (n=62) of survivors experienced moderate-to-severe fatigue out of 110 patients reporting fatigue. Thyroid functions were deranged in 22 patients (35.48%). The thyroid stimulating hormone (TSH) levels were found to have a significant negative association with the severity of fatigue, (P<0.05). Twelve patients (19.35%) had reduced DHEAS levels suggestive of impaired hormone synthesis in the adrenal gland. Twenty two postmenopausal survivors (35.48%) had raised oestradiol levels. Interpretation & conclusions: The findings of this study suggest that the hormonal milieu, especially thyroid hormone and DHEAS may have a role in CRF experienced by BCSs and needs further exploration.

Neuroprotective potential of biochanin-A and review of the molecular mechanisms involved.

Biochanin-A is a naturally occurring plant phytoestrogen, which mimics specific the agonistic activity of estrogens. Biochanin-A is known to possess numerous activities, including neuroprotective, anti-diabetic, hepatoprotective, anti-inflammatory, antioxidant, and antimicrobial activities, along with the anticancer activity. Neuroinflammation is thought to play a pivotal pathological role in neurodegenerative disease. Sustained neuroinflammatory processes lead to progressive neuronal damage in Parkinson's and Alzheimer's disease. Activation of PI3K/Akt cascade and inhibition of MAPK signaling cascade have been observed to be responsible for conferring protection against neuroinflammation in neurodegenerative diseases. An increased oxidative stress promotes neuronal apoptosis via potentiating the TLR-4/NF-κB and inhibiting PI3K/Akt signaling mediated increase in pro-apoptotic and decreases in antiapoptotic proteins. Various authors have explored biochanin-A's neuroprotective effect by using various cell lines and animal models. Biochanin-A has been reported to mediate its neuroprotective via reducing the level of oxidants, inflammatory mediators, MAPK, TLR-4, NF-κB, NADPH oxidase, AchE, COX-2 and iNOS. Whereas, it has been observed to increase the level of anti-oxidants, along with phosphorylation of PI3K and Akt proteins. The current review has been designed to provide insights into the neuroprotective effect of biochanin-A and possible signaling pathways leading to protection against neuroinflammation and apoptosis in the central nervous system. This review will be helpful in guiding future researchers to further explore biochanin A at a mechanistic level to obtain useful lead molecules.

Glycol chitosan stabilized nanomedicine of lapatinib and doxorubicin for the management of metastatic breast tumor.

Advanced breast cancer is known to be highly evasive to conventional therapeutic regimes with a 5-year survival rate of less than 30% compared to over 90% for early stages. Although several new approaches are being explored to improve the survival outcome, there is still some room for equipping existing drugs such as lapatinib (LAPA) and doxorubicin (DOX) to fight the systemic disease. LAPA is associated with poorer clinical outcomes in HER2-negative patients. However its ability to also target EGFR has warranted its use in recent clinical trials. Nevertheless, the drug is poorly absorbed post oral administration and possess low aqueous solubility. DOX on the other hand is avoided in vulnerable patients in advanced stages due to its pronounced off-target toxicity. To overcome the pitfalls of the drugs, we have fabricated a nanomedicine co-loaded with LAPA & DOX and stabilized with glycol chitosan, a biocompatible polyelectrolyte. With a loading content of ~ 11.5% and ~ 15% respectively, LAPA and DOX in a single nanomedicine showed synergistic action against triple-negative breast cancer cells in comparison to physically mixed free drugs. The nanomedicine showed a time-dependent association with cancer cells thereon inducing apoptosis leading to ~ 80% cell death. The nanomedicine was found to be acutely safe in healthy Balb/c mice and could negate DOX-induced cardio toxicity. The combination nanomedicine significantly inhibited both the primary 4T1 breast tumor and its spread to the lung, liver, heart, and kidney compared to pristine drug controls. These preliminary data indicate bright prospects for the nanomedicine to be effective against metastatic breast cancer.

Putative interactions between transthyretin and endosulfan II and its relevance in breast cancer.

The unregulated use of organochlorine pesticides (OCPs) has been linked to spread of breast cancer (BC), but the underlying biomolecular interactions are unknown. Using a case-control study, we compared OCP blood levels and protein signatures among BC patients. Five pesticides were found in significantly higher concentrations in breast cancer patients than in healthy controls: p',p' dichloro diphenyl trichloroethane (DDT), p'p' dichloro diphenyl dichloroethane (DDD), endosulfan II, delta-hexachlorocyclohexane (dHCH), and heptachlor epoxide A (HTEA). According to the odds ratio analysis, these OCPs, which have been banned for decades, continue to raise the risk of cancer in Indian women. Proteomic analysis of plasma from estrogen receptor-positive breast cancer patients revealed 17 dysregulated proteins, but transthyretin (TTR) was three times higher than in healthy controls, which is further validated by enzyme-linked immunosorbent assays (ELISA). Molecular docking and molecular dynamics studies revealed a competitive affinity between endosulfan II and the thyroxine-binding site of TTR, pointing towards the significance of the competition between thyroxin and endosulfan, resulting in endocrine disruption leading to breast cancer. Our study sheds light on the putative role of TTR in OCP-mediated BC, but more research is needed to decipher the underlying mechanisms that can be used to prevent the carcinogenic effects of these pesticides on women's health.

Crosstalk between protein kinase C α and transforming growth factor ß signaling mediated by Runx2 in intestinal epithelial cells.

Tight coordination of growth regulatory signaling is required for intestinal epithelial homeostasis. Protein kinase C α (PKCα) and transforming growth factor ß (TGFß) are negative regulators of proliferation with tumor suppressor properties in the intestine. Here, we identify novel crosstalk between PKCα and TGFß signaling. RNA-Seq analysis of nontransformed intestinal crypt-like cells and colorectal cancer cells identified TGFß receptor 1 (TGFßR1) as a target of PKCα signaling. RT-PCR and immunoblot analysis confirmed that PKCα positively regulates TGFßR1 mRNA and protein expression in these cells. Effects on TGFßR1 were dependent on Ras-extracellular signal-regulated kinase 1/2 (ERK) signaling. Nascent RNA and promoter-reporter analysis indicated that PKCα induces TGFßR1 transcription, and Runx2 was identified as an essential mediator of the effect. PKCα promoted ERK-mediated activating phosphorylation of Runx2, which preceded transcriptional activation of the TGFßR1 gene and induction of Runx2 expression. Thus, we have identified a novel PKCα→ERK→Runx2→TGFßR1 signaling axis. In further support of a link between PKCα and TGFß signaling, PKCα knockdown reduced the ability of TGFß to induce SMAD2 phosphorylation and cell cycle arrest, and inhibition of TGFßR1 decreased PKCα-induced upregulation of p21Cip1 and p27Kip1 in intestinal cells. The physiological relevance of these findings is also supported by The Cancer Genome Atlas data showing correlation between PKCα, Runx2, and TGFßR1 mRNA expression in human colorectal cancer. PKCα also regulated TGFßR1 in endometrial cancer cells, and PKCα, Runx2, and TGFßR1 expression correlates in uterine tumors, indicating that crosstalk between PKCα and TGFß signaling may be a common mechanism in diverse epithelial tissues.

A Comprehensive Review of Dilated Cardiomyopathy in Pre-clinical Animal Models in Addition to Herbal Treatment Options and Multi-modality Imaging Strategies.

Dilated cardiomyopathy (DCM) is distinguished by ventricular chamber expansion, systolic dysfunction, and normal left ventricular (LV) wall thickness, and is mainly caused due to genetic or environmental factors; however, its aetiology is undetermined in the majority of patients. The focus of this work is on pathogenesis, small animal models, as well as the herbal medicinal approach, and the most recent advances in imaging modalities for patients with dilated cardiomyopathy. Several small animal models have been proposed over the last few years to mimic various pathomechanisms that contribute to dilated cardiomyopathy. Surgical procedures, gene mutations, and drug therapies are all characteristic features of these models. The pros and cons, including heart failure stimulation of extensively established small animal models for dilated cardiomyopathy, are illustrated, as these models tend to procure key insights and contribute to the development of innovative treatment techniques for patients. Traditional medicinal plants used as treatment in these models are also discussed, along with contemporary developments in herbal therapies. In the last few decades, accurate diagnosis, proper recognition of the underlying disease, specific risk stratification, and forecasting of clinical outcome, have indeed improved the health of DCM patients. Cardiac magnetic resonance (CMR) is the bullion criterion for assessing ventricular volume and ejection fraction in a reliable and consistent direction. Other technologies, like strain analysis and 3D echocardiography, have enhanced this technique's predictive and therapeutic potential. Nuclear imaging potentially helps doctors pinpoint the causative factors of left ventricular dysfunction, as with cardiac sarcoidosis and amyloidosis.

Prevalence, Characteristics, and Correlates of Fatigue in Indian Breast Cancer Survivors: A Cross-Sectional Study.

Navneet KaurBackground Fatigue is one of the commonest sequelae of breast cancer treatment that adversely impacts quality of life (QOL) of breast cancer survivors (BCSs). However, very limited data are available about cancer-related fatigue in Indian patients. Hence, this study was planned with the objectives to study (1) prevalence of fatigue in short-, intermediate-, and long-term follow-up; (2) severity and characteristics of fatigue; (3) impact of fatigue on QOL; and (4) correlation of fatigue with other survivorship issues. Materials and Methods The study was conducted on ( n = 230) BCSs who had completed their primary treatment (surgery, radiotherapy, and chemotherapy) and were coming for follow-up. The prevalence of fatigue was noted from a screening tool, which comprised of 14 commonly reported survivorship issues. Assessment of fatigue was done by using survivorship fatigue assessment tool-1 score and QOL was assessed by functional assessment of cancer therapy-breast (FACT-B) questionnaires. To understand how fatigue evolved over time, survivors were divided into three groups according to the time elapsed since initial treatment: Group 1: <2 years ( n = 105); Group 2: 2-5 years ( n = 70); Group 3: >5 years ( n = 55). Statistical Analysis Data was analyzed by using simple descriptive statistics, one way analysis of variance followed by Tukey's test for comparison of quantitative data among the three groups, and Pearson correlation coefficients for association of fatigue with other survivorship issues. Results Clinically significant fatigue (≥4) was noted in 38% of BCSs. However, high overall prevalence of fatigue (60%) was seen, which persisted in long-term survivors (51%) as well. Severity of fatigue was mostly mild (37.7%) to moderate (47.1%). Fatigue scores were significantly higher in short-term survivors ( 5.01 ± 2.06) than intermediate- (4.03 ± 1.42) and long-term BCSs (3.57 ± 1.37). The mean score on FACT-B was 90.07 ± 10.17 in survivors with fatigue and 104.73 ± 7.13 in those without fatigue ( p = 0.000). Significant correlation of fatigue was seen with other survivorship issues like limb swelling, chronic pain, premature menopause, and its related symptoms and emotional distress. Conclusion Fatigue is highly prevalent in BCSs. Survivorship care programs should include appropriate measures to evaluate and address fatigue.

Bacterial exopolysaccharides as emerging bioactive macromolecules: from fundamentals to applications.

Microbial exopolysaccharides (EPS) are extracellular carbohydrate polymers forming capsules or slimy coating around the cells. EPS can be secreted by various bacterial genera that can help bacterial cells in attachment, environmental adaptation, stress tolerance and are an integral part of microbial biofilms. Several gut commensals (e.g., Lactobacillus, Bifidobacterium) produce EPS that possess diverse bioactivities. Bacterial EPS also has extensive commercial applications in the pharmaceutical and food industries. Owing to the structural and functional diversity, genetic and metabolic engineering strategies are currently employed to increase EPS production. Therefore, the current review provides a comprehensive overview of the fundamentals of bacterial exopolysaccharides, including their classification, source, biosynthetic pathways, and functions in the microbial community. The review also provides an overview of the diverse bioactivities of microbial EPS, including immunomodulatory, anti-diabetic, anti-obesity, and anti-cancer properties. Since several gut microbes are EPS producers and gut microbiota helps maintain a functional gut barrier, emphasis has been given to the intestinal-level bioactivities of the gut microbial EPS. Collectively, the review provides a comprehensive overview of microbial bioactive exopolysaccharides.

Computational analysis of protein-protein interaction network of differentially expressed genes in benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is a commonly occurring disease in aging men. It involves cellular proliferation of stromal and glandular tissues leading to prostate enlargement. Current drug therapies show several adverse effects such as sexual dysfunctions and cardiovascular side effects. Therefore, there is a need to develop more effective medical treatment for BPH. In this regard, we aimed to identify genes which play a critical role in BPH. We have obtained the dataset of differentially expressed genes (DEGs) of BPH from NCBI GEO. DEGs were investigated in the context of their protein-protein interactions (PPI). Hub genes i.e. genes associated with BPH were scrutinized based on the topological parameters of the PPI network. These were analyzed for functional annotations, pathway enrichment analysis and transcriptional regulation. In total, 38 hub genes were identified. Hub genes such as transcription factor activator protein-1 and adiponectin were found to play key roles in cellular proliferation and inflammation. Another gene peroxisome proliferator activated receptor gamma was suggested to cause obesity, a common comorbidity of BPH. Moreover, our results indicated an important role of transforming growth factor-beta (TGF-ß) signaling and smooth muscle cell proliferation which may be responsible for prostate overgrowth and associated lower urinary tract symptoms frequently encountered in BPH patients. Zinc finger protein Snai1 was the most prominent transcription factor regulating the expression of hub genes that participate in TGF-ß signaling. Overall, our study has revealed significant hub genes that can be employed as drug targets to develop potential therapeutic interventions to treat BPH.