Understanding the role of miRNAs in cervical cancer pathogenesis and therapeutic responses.

Cervical cancer (CC) is the most common cancer in women and poses a serious threat to health. Despite familiarity with the factors affecting its etiology, initiation, progression, treatment strategies, and even resistance to therapy, it is considered a significant problem for women. However, several factors have greatly affected the previous aspects of CC progression and treatment in recent decades. miRNAs are short non-coding RNA sequences that regulate gene expression by inhibiting translation of the target mRNA. miRNAs play a crucial role in CC pathogenesis by promoting cancer stem cell (CSC) proliferation, postponing apoptosis, continuing the cell cycle, and promoting invasion, angiogenesis, and metastasis. Similarly, miRNAs influence important CC-related molecular pathways, such as the PI3K/AKT/mTOR signaling pathway, Wnt/ß-catenin system, JAK/STAT signaling pathway, and MAPK signaling pathway. Moreover, miRNAs affect the response of CC patients to chemotherapy and radiotherapy. Consequently, this review aims to provide an acquainted summary of onco miRNAs and tumor suppressor (TS) miRNAs and their potential role in CC pathogenesis and therapy responses by focusing on the molecular pathways that drive them.

Exploring the Potential of Ellagic Acid in Gastrointestinal Cancer Prevention: Recent Advances and Future Directions.

Gastrointestinal (GI) cancers are a significant global health concern with diverse etiologies and limited treatment options. Ellagic acid (EA), a natural polyphenolic compound, exhibits promising anticancer properties against various GI malignancies. In this article, we have reviewed recent research on the anticancer potential of EA across esophageal, gastric, colorectal, pancreatic, and liver cancers. In esophageal cancer, EA inhibits the formation of O6-methylguanine (O6-meGua) adducts induced by carcinogens like N-nitrosomethylbenzylamine (NMBA), thereby suppressing tumor growth. Additionally, EA inhibits STAT3 signaling and stabilizes tumor suppressor proteins, showing potential as an anti-esophageal cancer agent. In gastric cancer, EA regulates multiple pathways involved in cell proliferation, invasion, and apoptosis, including the p53 and PI3K-Akt signaling pathways. It also demonstrates anti-inflammatory and antioxidant effects, making it a promising therapeutic candidate against gastric cancer. In colorectal cancer (CRC), EA inhibits cell proliferation, induces apoptosis, and modulates the Wnt/ß-catenin and PI3K/Akt pathways, suggesting its efficacy in preventing CRC progression. Furthermore, EA has shown promise in pancreatic cancer by inhibiting nuclear factor-kappa B, inducing apoptosis, and suppressing epithelial-mesenchymal transition. In liver cancer, EA exhibits radio-sensitizing effects, inhibits inflammatory pathways, and modulates the tumor microenvironment, offering potential therapeutic benefits against hepatocellular carcinoma. Studies on EA potential in combination therapies and the development of targeted delivery systems are required for enhanced efficacy against gastrointestinal cancers.

Neighborhood Disadvantage and Prostate Tumor Aggressiveness among African American and European American Men.

BACKGROUND: Studies have identified associations between neighborhood disadvantage (ND), which is more likely to affect African American (AA) individuals, and aggressive prostate cancer. Thus, ND may contribute to prostate cancer disparities. However, it is unknown what ND components drive aggressive disease and whether associations vary by race. METHODS: We evaluated associations between aggressive prostate cancer and four ND metrics-Area Deprivation Index (ADI), validated Bayesian Neighborhood Deprivation Index (NDI), racial isolation (RI) index, and historical redlining, and whether these factors interacted with race, among men with prostate cancer treated at the University of Maryland Greenebaum Comprehensive Cancer Center (2004-2021). RESULTS: We included 1,458 men (698 European American and 760 AA). AA men were more likely to experience ND. In adjusted models, the ADI, RI, and redlining were significantly associated with aggressive versus nonaggressive prostate cancer overall [ADI, OR for one SD increase = 1.14, 95% confidence interval (CI), 1.00-1.30; RI, OR = 1.27, CI, 1.07-1.51; redlining, OR = 1.77; CI, 1.23-2.56] and among AA men. The NDI was associated with aggressive prostate cancer among AA men (OR = 1.32, 95% credible interval: 1.13-1.57); percent in poverty received the largest importance weight. The ADI (P heterogeneity = 0.002) and NDI (exceedance probability heterogeneity = 98.1%) significantly interacted with race, such that associations were significantly stronger for AA men. CONCLUSIONS: We identified novel significant positive associations for racial segregation and historical redlining with aggressive prostate cancer and significant interactions between ND indices and race. IMPACT: Findings inform specific ND components that are associated with aggressive prostate cancer and suggest the ND effect is stronger for AA men, which has implications for interventions to reduce disparities.

Preparation, characterization and functional evaluation of soy protein isolate-peach gum conjugates prepared by wet heating Maillard reaction.

This study was conducted to formulate a conjugate of soy protein isolate (SPI) and peach gum (PG) with improved functional properties, interacting at mass ratios of 1:1, 1:2, 1:3, 2:1, and 2:3 by Maillard reaction via wet heating method. Conjugation efficiency was confirmed by grafting degree (DG) and browning index (BI). Results indicated that DG increased with increasing concentration of PG, and decreased with increasing pH, whereas no remarkable change was observed with increasing reaction time. The conjugates were optimized at a ratio of 1:3. SDS-PAGE confirmed conjugate formation, Fourier transform infrared spectroscopy (FTIR) and circular dichroism (CD) verified conjugate secondary structural changes, and scanning electron microscopy (SEM) indicated significant overall structural changes. The functional properties, solubility, emulsifying stability, water holding, foaming, and antioxidant activity were significantly improved. This study revealed the wet heating method as an effective approach to improve the functional properties of soy protein.

Overview of Unilateral and Bilateral Pediatric Facial Paralysis: Workup, Treatment, and Frontiers.

Pediatric facial nerve paralysis can present significant challenges based on its various etiologies, unique approach to treatment options, and overall outcomes. It can impact both the child and parent when regarding function, appearance, and psychosocial implications. The etiology of facial nerve palsy can include congenital, traumatic, iatrogenic, and idiopathic causes. In some, the paralysis is transient while others have permanent loss of function. A thorough evaluation and differential diagnosis are essential to guide treatment planning. The purpose of this paper is to review facial paralysis in children with a focus on surgical management.

Neighborhood Disadvantage and Prostate Tumor RNA Expression of Stress-Related Genes.

Importance: African American men experience greater prostate cancer incidence and mortality than White men. Growing literature supports associations of neighborhood disadvantage, which disproportionately affects African American men, with aggressive prostate cancer; chronic stress and downstream biological impacts (eg, increased inflammation) may contribute to these associations. Objective: To examine whether several neighborhood disadvantage metrics are associated with prostate tumor RNA expression of stress-related genes. Design, Setting, and Participants: This cross-sectional study leveraged prostate tumor transcriptomic data for African American and White men with prostate cancer who received radical prostatectomy at the University of Maryland Medical Center between August 1992 and January 2021. Data were analyzed from May 2023 to April 2024. Exposures: Using addresses at diagnosis, 2 neighborhood deprivation metrics (Area Deprivation Index [ADI] and validated bayesian Neighborhood Deprivation Index) as well as the Racial Isolation Index (RI) and historical redlining were applied to participants' addresses. Self-reported race was determined using electronic medical records. Main Outcomes and Measures: A total of 105 stress-related genes were evaluated with each neighborhood metric using linear regression, adjusting for race, age, and year of surgery. Genes in the Conserved Transcriptional Response to Adversity (CTRA) and stress-related signaling genes were included. Results: A total of 218 men (168 [77%] African American, 50 [23%] White) with a median (IQR) age of 58 (53-63) years were included. African American participants experienced greater neighborhood disadvantage than White participants (median [IQR] ADI, 115 [100-130] vs 92 [83-104]; median [IQR] RI, 0.68 [0.34-0.87] vs 0.11 [0.06-0.14]). ADI was positively associated with expression for 11 genes; HTR6 (serotonin pathway) remained significant after multiple-comparison adjustment (ß = 0.003; SE, 0.001; P < .001; Benjamini-Hochberg q value = .01). Several genes, including HTR6, were associated with multiple metrics. We observed higher expression of 5 proinflammatory genes in the CTRA with greater neighborhood disadvantage (eg, CXCL8 and ADI, ß = 0.008; SE, 0.003; P = .01; q value = .21). Conclusions and Relevance: In this cross-sectional study, the expression of several stress-related genes in prostate tumors was higher among men residing in disadvantaged neighborhoods. This study is one of the first to suggest associations of neighborhood disadvantage with prostate tumor RNA expression. Additional research is needed in larger studies to replicate findings and further investigate interrelationships of neighborhood factors, tumor biology, and aggressive prostate cancer to inform interventions to reduce disparities.

Identification of plant based potential antifungal compounds against BMK-1 protein of Bipolaris oryzae using molecular docking approach.

Rice brown spot is an important disease of rice worldwide that inflicts substantial yield losses. The antimicrobial potential of methanol, acetone and dimethyl sulfoxide (DMSO) extracts of different medicinal plants, viz., Syzygium aromaticum, Saussurea costus, Acorus calamus, Bergenia ciliate, Geranium pratense, Mentha longifolia, Inula racemosa, Podophyllum hexandrum, Heracleum candicans and Picrorhiza kurroa, against the brown spot pathogen Bipolaris oryzae in vitro was evaluated via mycelial growth inhibition and spore germination inhibition assays. Among the plant extracts tested, 100% mycelial inhibition was observed for the methanol extract of Syzygium aromaticum at all three concentrations (2000 ppm, 3000 ppm and 4000 ppm), followed by the methanol extract of Inula racemosa (90.33%) at 4000 ppm. A maximum conidial germination inhibition of 83.54% was exhibited by the Heracleum candicans leaf extract. Phytochemical profiling of Syzygium aromaticum and Inula racemosa through liquid chromatography and mass spectrometry (HR-LCMS) revealed the presence of several compounds, such as eugenol, ursolic acid, quercetin, chlorogenic acid, and noscapine. A molecular docking approach was used to identify key inhibitory molecules against B. oryzae. Among the compounds detected in S. aromaticum and Inula racemosa, ursolic acid and noscapine were found to have the greatest binding affinity for the Big Mitogen Activated Protein Kinase (BMK-1) enzyme present in B. oryzae. In conclusion, S. aromaticum and Inula racemosa are potent compounds that could serve as lead compounds for drug discovery in the future.

USP11 promotes prostate cancer progression by up-regulating AR and c-Myc activity.

Androgen receptor (AR) is a main driver for castration-resistant prostate cancer (CRPC). c-Myc is an oncogene underlying prostate tumorigenesis. Here, we find that the deubiquitinase USP11 targets both AR and c-Myc in prostate cancer (PCa). USP11 expression was up-regulated in metastatic PCa and CRPC. USP11 knockdown (KD) significantly inhibited PCa cell growth. Our RNA-seq studies revealed AR and c-Myc as the top transcription factors altered after USP11 KD. ChIP-seq analysis showed that either USP11 KD or replacement of endogenous USP11 with a catalytic-inactive USP11 mutant significantly decreased chromatin binding by AR and c-Myc. We find that USP11 employs two mechanisms to up-regulate AR and c-Myc levels: namely, deubiquitination of AR and c-Myc proteins to increase their stability and deubiquitination of H2A-K119Ub, a repressive histone mark, on promoters of AR and c-Myc genes to increase their transcription. AR and c-Myc reexpression in USP11-KD PCa cells partly rescued cell growth defects. Thus, our studies reveal a tumor-promoting role for USP11 in aggressive PCa through upregulation of AR and c-Myc activities and support USP11 as a potential target against PCa.

Delineating the Antiapoptotic Property of Apigenin as an Antitumor Agent: A Computational and In Vitro Study on HeLa Cells.

Apigenin, a flavonoid, is reported to have multiple health benefits including cancer prevention; this study evaluates the drug likeliness and Swiss ADME properties of apigenin. Apoptosis, which is a key hallmark of cancer, is associated with the deregulation of the balance between proapoptotic proteins and antiapoptotic proteins such as BCL-2,BCL-xl, BFL-1, BCL-w, BRAG-16, and MCL-1. The docking studies of apigenin with the mentioned proteins was performed to identify the interactions between the ligand and proteins, which suggested that apigenin was able to bind to most of the proteins similar to the inhibitory molecules of its native structure. A remarkable reduction in the total energy after energy minimization of apigenin-antiapoptotic protein complexes suggested increased stability of the docked complexes. The same complexes were found to be stable over a 10 ns period of molecular simulation at 300 K. These findings advocated the study to evaluate apigenin's potential to inhibit the HeLa cells at 5, 10, and 15 µM concentrations in the clonogenic assay. Apigenin inhibited the colony-forming ability of HeLa cells in a dose-dependent manner over a fortnight. Light microscopy of the treated cells displayed the morphological evidence characteristic of apoptosis in HeLa cells such as blebbing, spike formation, cytoplasmic oozing, and nuclear fragmentation. Thus, these results clearly indicate that apigenin may be used as a potential chemopreventive agent in cervical cancer management.

Smoking behaviour in post-acute myocardial infarction patients: cross-sectional study.

Introduction: Heart disease remains the leading cause of death in developed countries, and cigarette smoking contributes to a significant proportion of cardiovascular-related deaths. Abstaining from tobacco use is associated with a significant reduction in the risk of recurrent myocardial infarctions. Methodology: In this cross-sectional study, 384 participants post-acute myocardial infarction (MI) were recruited through random sampling to explore the associations between smoking status and intention to quit smoking. Data collection took place over a 6-month period at a tertiary care hospital, Islamabad, Pakistan. Results: The majority of participants were male (59.9%) and fell into the age category of 46-50 years (37.5%). Heavy daily smokers comprised the largest smoking group (41.6%), and non-ST-elevated MI was the most common subtype (40.1%). Intention to quit smoking varied among participants, with the pre-contemplation stage having the highest representation (19.3%), followed by contemplation (25.8%). Notably, a significant proportion of participants expressed no intention to quit smoking (35.4%). Conclusion: Multinomial logistic regression analysis identified current smoking as a significant predictor of intention to quit in the preparation and contemplation stages. Overall, this study underscores the importance of considering smoking behaviour when evaluating the intention to quit smoking post-MI and highlights the need for tailored interventions and support strategies to address smoking cessation in this population. These findings offer valuable insights for the development of effective strategies aimed at reducing persistent smoking following MI and improving patient outcomes.

Targeting androgen biosynthesis in prostate cancer: implications on endocrine physiology.

PURPOSE OF REVIEW: Targeting specific steroidogenic enzymes is effective in decreasing testosterone synthesis, resulting in significant antitumor effects in prostate cancer. Such treatments result in disruptions of complicated and intertwining pathways with systemic physiologic consequences via effects on the adrenal gland and renin-angiotensin-aldosterone axis. This review highlights some of these aspects that need to be taken into consideration when treating patients with androgen biosynthesis inhibitors. RECENT FINDINGS: Targeting CYP17A1, a key enzyme involved in androgen biosynthesis, is a well established treatment in prostate cancer. More recently, efforts are underway to target a gatekeeper enzyme of steroidogenesis, CYP11A1. This enzyme mediates conversion of cholesterol to pregnenolone, the first step in steroid hormone biogenesis. Studies are beginning to demonstrate antitumor effects of ODM-208, a CYP11A1 inhibitor in prostate cancer. Although anticipated to have a therapeutic role in prostate cancer, there are potential downstream effects of CYP11A1 targeting arising from suppression of the entire adrenal cortex, including long-term adrenal insufficiency and possibly cardiovascular dysregulation. SUMMARY: Agents targeting androgen biosynthesis can have systemic implications. Balancing management of prostate cancer with better understanding of the mechanisms associated with potential side effects will allow for patients to obtain improved antitumor benefit while mitigating against treatment-associated adverse effects.

Facile synthesis of substituted 2-aroylbenzo[b]thiophen-3-ols to form novel triazole hybrids using click chemistry.

An efficient one-pot method is proposed for the synthesis of 2-aroylbenzo[b]thiophen-3-ols from 2-mercaptobenzoic acid and various substituted aryl bromomethyl ketones in the presence of triethylamine. The reaction is likely to proceed through SN2-type nucleophilic attack of the sulfhydryl group in thiosalicylic acid on bromomethyl ketone in the presence of a base to afford sulfanylbenzoic acid, which undergoes an intramolecular cyclization in situ to furnish 2-aroylbenzo[b]thiophen-3-ol in high yield. To investigate the utility of the synthesized benzothiophene scaffold, an alkyne moiety was introduced at the 3-hydroxy position and subsequently subjected to a click reaction to form novel benzothiophene-triazole hybrids in good yields. A simple and straightforward approach to synthesizing 2-aroylbenzo[b]thiophen-3-ols can open new avenues for discovering novel biological and pharmaceutical compounds.

Corneal Neurotization: Essentials for The Facial Paralysis Surgeon.

Deficits in corneal innervation lead to neurotrophic keratopathy (NK). NK is frequently associated with facial palsy, and corneal damage can be accelerated by facial palsy deficits. Corneal nerves are important regulators of limbal stem cells, which play a critical role in epithelial maintenance and healing. Nonsurgical treatments of NK have undergone recent innovation, and growth factors implicated in corneal epithelial renewal are a promising therapeutic avenue. However, surgical intervention with corneal neurotization (CN) remains the only definitive treatment of NK. CN involves the transfer of unaffected sensory donor nerve branches to the affected cornea, and a variety of donor nerves and approaches have been described. CN can be performed in a direct or indirect manner; employ the supraorbital, supratrochlear, infraorbital, or great auricular nerves; and utilize autograft, allograft, or nerve transfer alone. Unfortunately, comparative studies of these factors are limited due to the procedure's novelty and varied recovery timelines after CN. Regardless of the chosen approach, CN has been shown to be a safe and effective procedure to restore corneal sensation and improve visual acuity in patients with NK.

Acute kidney injury in birth asphyxiated patients: A cross sectional study at Bahawal Victoria Hospital.

BACKGROUND: The presence of perinatal asphyxia and its severity appear to correlate with increasing incidence of Acute kidney injury (AKI). The objective of this study is to determine the frequency of AKI and its outcome in birth asphyxia. METHODS: This cross-sectional study was carried out in the Department of Pediatric Medicine from March 2019 to September 2019. A total of 111 newborns with birth asphyxia of gestational age 37-41 weeks were included. Neonates born to mothers having hypertension and diabetes mellitus, patients with congenital kidney anomalies like polycystic kidney disease and renal agenesis, and mothers taking nephrotoxic drugs or any other known cause of AKI like hypovolemic shock were excluded. Urine output (UOP) and final outcome of the patient were also noted. AKI was noted. RESULTS: The mean gestational age was 38.29 ± 1.07 weeks. The mean weight of neonates was 3.08 ± 0.31 kg. The frequency of AKI in birth asphyxia was 20 (18.02%) neonates. Complete recovery in AKI patients was seen in 07 (35.0%) and death in 13 (65.0%) patients. CONCLUSION: This study has shown that the frequency of AKI in birth asphyxia was found in 18.02% neonates with complete recovery seen in 35.0% and death in 65.0% patients.

Gender differences in the surgical management of trachomatous trichiasis: an exploratory analysis of global trachoma survey data, 2015-2019.

BACKGROUND: Trachomatous trichiasis (TT) is a painful, potentially blinding eye condition that can be managed through epilation or surgery. Women are affected by TT approximately twice as often as men and are believed to face gendered barriers to receiving surgical care to prevent vision loss. METHODS: We used data from 817 cross-sectional surveys conducted during 2015-2019 in 20 African countries to estimate the prevalence difference (PD) between female and male eyes for four outcomes potentially indicating gender-related differences in TT management: (1) received surgery and developed postoperative TT (PTT), (2) never offered surgery, (3) offered surgery but declined it, and (4) offered epilation but never offered surgery. RESULTS: The prevalence was modestly elevated among female eyes compared with male eyes for having PTT (PD:1.8 [95% confidence limits (CL): 0.6, 3.0]) and having declined surgery for the eye (PD: 6.2 [95% CL: 1.8, 10.7]). The proportion offered epilation was similar by gender (PD:0.5 [95% CL: -0.4, 1.3]), while never having been offered surgery was somewhat more prevalent among male eyes (PD: -2.1 [95% CL: -3.5, -0.7]). CONCLUSIONS: Our results suggest potential gender differences in TT management. More research is needed to determine the causes and implications of the observed differences.

Prospects of earthworm coelomic fluid as a potential therapeutic agent to treat cancer.

Cancer is a major public health concern because it is one of the main causes of morbidity and mortality worldwide. As a result, numerous studies have reported the development of new therapeutic compounds with the aim of selectively treating cancer while having little negative influence on healthy cells. In this context, earthworm coelomic fluid has been acknowledged as a rich source of several bioactive substances that may exhibit promising anticancer activity. Therefore, the objective of the present review is to evaluate the findings of the reported studies exploring the antitumor effects of coelomic fluid in the context of its possible utilization as a natural therapeutic agent to cure different types of cancer. The possible mechanisms underlying the coelomic fluid's anticancerous potential as well as the possibility for future development of cutting-edge therapeutic agents utilizing coelomic fluid-derived natural bioactive compounds to treat cancer disorders have been discussed along with future challenges. In addition, the feasibility of encapsulation of bioactive compounds derived from coelomic fluid with nanomaterials that could be further explored to attain more effective anticancer competence is discussed.

Co-administration of Chrysin and Luteolin with Cisplatin and Topotecan Exhibits a Variable Therapeutic Value in Human Cancer Cells, HeLa.

Combinational treatment is a promising strategy for better cancer treatment outcomes. Chrysin and luteolin have demonstrated effective anticancer activity. Cisplatin and topotecan are commonly used for the treatment of human cancers. However, various side effects including drug resistance are an imperative restriction to use them as pharmacological therapy. Therefore, the aim was to use these agents in combination with flavones for better efficacy. In the present study, it was found that the combination of chrysin and cisplatin and luteolin and cisplatin significantly improved the anticancer effect as both the combinations showed synergistic interactions [combinational index (CI < 1)]. Remarkably, the combination of chrysin and luteolin with topotecan depicted the antagonistic interaction (CI > 1). Further, increased expression of the pro-apoptotic proteins Bax and caspase 8 and the inhibition of the antiapoptotic protein Bcl-2 were instituted in the synergistic doses (chrysin + cisplatin and luteolin + cisplatin), hence promoting apoptosis. Also, it was found that the synergistic combination inhibited the migration of HeLa cells by downregulation of metalloproteases and upregulation of TIMPs. However, there are no significant changes depicted in the antagonistic combinations which support their role in their antagonistic effects. Based on these results, it can be inferred that the two or more drug combinations need to be explored well for their interaction to enhance the therapeutic outcomes.

Melittin: a possible regulator of cancer proliferation in preclinical cell culture and animal models.

BACKGROUND: Melittin is a water-soluble cationic peptide derived from bee venom that has been thoroughly studied for the cure of different cancers. However, the unwanted interactions of melittin produce hemolytic and cytotoxic effects that hinder their therapeutic applications. To overcome the shortcomings, numerous research groups have adopted different approaches, including conjugation with tumor-targeting proteins, gene therapy, and encapsulation in nanoparticles, to reduce the non-specific cytotoxic effects and potentiate their anti-cancerous activity. PURPOSE: This article aims to provide mechanistic insights into the chemopreventive activity of melittin and its nanoversion in combination with standard anti-cancer drugs for the treatment of cancer. METHODS: We looked over the pertinent research on melittin's chemopreventive properties in online databases such as PubMed and Scopus. CONCLUSION: In the present article, the anti-cancerous effects of melittin on different cancers have been discussed very nicely, as have their possible mechanisms of action to act against different tumors. Besides, it interacts with different signal molecules that regulate the diverse pathways of cancerous cells, such as cell cycle arrest, apoptosis, metastasis, angiogenesis, and inflammation. We also discussed the recent progress in the synergistic combination of melittin with standard anti-cancer drugs and a nano-formulated version of melittin for targeted delivery to improve its anticancer potential.