Therapy resistance in prostate cancer: mechanism, signaling and reversal strategies.

Prostate cancer (PC) depicts a major health challenge all over the globe due to its complexities in the treatment and diverse clinical trajectories. Even in the advances in the modern treatment strategies, the spectrum of resistance to the therapies continues to be a significant challenge. This review comprehensively examines the underlying mechanisms of the therapy resistance occurred in PC, focusing on both the tumor microenvironment and the signaling pathways implicated in the resistance. Tumor microenvironment comprises of stromal and epithelial cells, which influences tumor growth, response to therapy and progression. Mechanisms such as microenvironmental epithelial-mesenchymal transition (EMT), anoikis suppression and stimulation of angiogenesis results in therapy resistance. Moreover, dysregulation of signaling pathways including androgen receptor (AR), mammalian target of rapamycin/phosphoinositide 3 kinase/AKT (mTOR/PI3K/AKT), DNA damage repair and Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathways drive therapy resistance by promoting tumor survival and proliferation. Understanding these molecular pathways is important for developing targeted therapeutic interventions which overcomes resistance. In conclusion, a complete grasp of mechanisms and pathways underlying medication resistance in PC is important for the development of individualized treatment plans and enhancements of clinical outcomes. By studying and understanding the complex mechanisms of signaling pathways and microenvironmental factors contributing to therapy resistance, this study focuses and aims to guide the development of innovative therapeutic approaches to effectively overcome the PC progression and improve the survival rate of patients.

Fluoride Ion Storage and Conduction Mechanism in Fluoride Ion Battery Positive Electrode, Ruddlesden-Popper-Type Layered Perovskite La1.2Sr1.8Mn2O7 Crystal.

Structural characteristics on fluoride ion storage and conduction mechanism in La1.2Sr1.8Mn2O7, and its fluoridated materials, La1.2Sr1.8Mn2O7F and La1.2Sr1.8Mn2O7F2, for an all-solid-state fluoride ion battery positive electrode with a high volumetric capacity surpassing those of lithium-ion ones have been revealed using the Rietveld method and maximum entropy method. In La1.2Sr1.8Mn2O7, once the F- ions are taken into the NaCl slabs in its crystal through the charging process, it forms two stable fluoride compounds, La1.2Sr1.8Mn2O7F and La1.2Sr1.8Mn2O7F2, with the help of the Mn oxidation reaction. In these oxyfluorides, thermal vibrations of the F- ions inserted are much larger, especially in the a-b plane, than along the c axis. When surplus energy, such as an electric field for charging, is applied to these crystals at near room temperature or higher, the anions immediately begin to jump to their neighboring lattice sites, resulting in sufficiently rapid and large ionic conduction. The MEM analyses and density functional theory (DFT) calculations have revealed that the F- ions enable to easily travel along the ⟨110⟩ directions in the NaCl slabs of these crystals. These structural features thus make La1.2Sr1.8Mn2O7 and its fluorides possess both of two features incompatible with each other, ion storage and conduction, indispensable for rechargeable batteries.

Fluoride-Induced Alterations in the Pancreas of Mammals: A Meta-analysis.

This review explores the diverse effects of fluoride on pancreatic function, encompassing both in vitro and in vivo studies. Fluoride exposure induces notable alterations at the cellular and molecular levels, affecting pancreatic morphology, histology, and enzymatic activity. In vitro studies demonstrate significant inhibition of pancreatic α-amylase activity and apoptosis in pancreatic beta cells. In vivo investigations reveal structural abnormalities in pancreatic cells, including mitochondrial damage, vacuolation, and nuclear damage. Moreover, fluoride exposure disrupts antioxidant enzyme activity, exacerbating oxidative stress and lipid peroxidation. Changes in digestive enzyme activity, such as the inhibition of pancreatic lipase and α-amylase, further contribute to pancreatic dysfunction. Additionally, alterations in hormone secretion, notably insulin levels and disturbed glucose homeostasis, highlight the complex effects of fluoride on the pancreatic endocrine system. These findings underscore fluoride-induced pancreatic toxicity and highlight the need for a comprehensive understanding and mitigation strategies to safeguard pancreatic health.

Label-Free Assessment of Neuron-Specific Enolase via Polydopamine over a Carbon-Nanotube-Based Flexible Immunosensor.

A label-free electrochemical immunosensor was developed for the rapid and sensitive detection of neuron-specific enolase (NSE). The electropolymerization of dopamine in conjunction with highly conductive carbon nanotubes offers a simple and quick platform for the direct anchoring of antibodies without the assistance of any coupling agent as well as a blocking agent. The developed immunosensor exhibited a wider detection range from 120 pM (9 ng mL-1) to 3 nM (200 ng mL-1) for NSE with a high sensitivity of 3.9 µA pM-1 cm-2 in 0.1 M phosphate-buffered saline (PBS) at physiological pH (7.4). Moreover, the short recognition time (15 min) for the antigen enabled the detection to be fast and less invasive. Additionally, the evaluation of a rate constant at various concentrations of NSE via feedback mode of scanning electrochemical microscopy (SECM) explained the profound effect of antigen concentration on the rate of flow of electrons. Therefore, the proposed immunosensor can be a promising tool for the early detection of small cell lung cancer in a very short period of time with consistent accuracy.

Lymphocytic infiltration as a marker of disease severity in patients with bullous pemphigoid-A case series.

Patients of Bullous Pemphigoid with predominant lymphocytic inflammatory infiltrate on histopathology have a severe form of the disease requiring high doses of steroids along with an adjuvant immunosuppressant. Thus, the histopathological evaluation would predict the severity of Bullous Pemphigoid, especially in countries where ELISA and immunofluorescence are not readily available.

Effects of Fluoride Toxicity on Female Reproductive System of Mammals: A Meta-Analysis.

Considerable integrative efforts have been made to investigate the effects of fluoride on female reproductive organs since the last years. The ingestion of fluoride causes adverse effects on human health like causing skeletal fluorosis, dental fluorosis, bone fractures, kidney problems, decrease birth rates, weakening of thyroid functionality, and impair intelligence, particularly in children. In this review, we discuss the adverse effects of fluoride on female reproductive organs and presented certain remedies. A total of 53 papers on the effect of fluoride on female reproductive organs, including 6 population surveys were examined. Google Scholar, Google, Research Gate, PubMed, and the International Journal of Fluoride have all been searched for fluoride research papers. Various doses and pathological effects have been described in this review article.

Misuse of topical over-the-counter medication: A case report.

Overuse of topical medication is a national issue. Over-the-counter (OTC) medications are dispensed to patients directly without a physician's prescription and when used improperly without proper knowledge can lead to their misuse and toxicity.

Ganoderma lucidum: Insights on host range, diagnosis, and management strategies.

Forest ecosystems play an important role in upholding life on our planet. However, the onslaught of fungal pathogens like Ganoderma lucidum, poses a threat by decimating numerous tree species. G. lucidum identified as a root pathogen, causing root rot in numerous tree species of horticulture and forestry importance. The fungus initiates infection through basidiospores, which germinate and penetrate within roots and start to degrade lignocellulosic components of plant cells. Early-stage detection of G. lucidum, is challenging, while in advance stages, the wood undergoes softening and a loss of tensile strength, rendering the disease incurable. Hence, effective management of G. lucidum necessitates a pivotal role of disease diagnostic techniques, which are currently underutilized or inadequately accessible. Subsequent implementation of suitable control measures becomes imperative to thwart disease occurrence and mitigate its impact in early stages, thus preserving the vitality of forest ecosystems. This study provides comprehensive overview of G. lucidum, covering taxonomy, pathogenicity, disease cycle, diagnosis and effective control measures, which will be helpful in formulating effective diagnostic techniques for early management of root rot disease.

Granulosis rubra nasi: A rare dermatosis not limited to nose.

Granulosis rubra nasi (GRN) is a rare genodermatosis involving the eccrine glands with an unknown aetiology. It is clinically characterized by localized hyperhidrosis, erythema, papules, pustules, and vesicles over central region of face and usually manifests during early childhood. GRN is asymptomatic, spontaneously resolves during puberty, and treatment options have inconsistent results. We hereby present a case of GRN in 38 years female with sites and dermoscopy findings not defined so far.

Metabolic syndrome in patients with lichen planus: A case-control study.

Background: Lichen Planus (LP) is a chronic dermatosis affecting the skin and mucous membranes. Chronic inflammation and oxidative stress in patients with LP is a trigger predisposing to Metabolic Syndrome. Objectives: To study the association of Metabolic Syndrome in patients with LP. Materials and Methods: A hospital-based prospective case-control study was conducted from April 2021 to January 2023 including 75 histopathologically confirmed patients with LP and 82 age and sex-matched controls according to the inclusion and exclusion criteria. Metabolic Syndrome was diagnosed using Modified National Cholesterol Education Programme Adult Treatment Panel III criteria. Statistical analysis of the data was performed using Statistical Package for the Social Sciences software, version 26. The chi-square test was used for data analysis. Results: The majority (30.6%) of the patients belonged to the age group 31-40 years. The mean age of patients with LP was 46.13 ± 14.9 years. Female predominance (69.3%) was observed in our study. Patients with classic LP (54.6%) were predominantly observed. Metabolic Syndrome was significantly prevalent in LP patients than in controls (32% vs. 13.4%, p = 0.005, OR 3.037) and was significantly associated with morphology (only oral mucosal involvement, 61.5%, p 0.027, OR 3.9), severity (severe LP, 58.6%, p < 0.001, OR 7.79), and duration of the disease (≥6 months, 55.5%, p 0.001, OR 5.42). 71% of Metabolic Syndrome was observed in females (p 0.847). Among patients with metabolic syndrome, the majority belonged to the age group between 31 and 40 years (37.5%, p 0.378). Systolic and Diastolic Blood Pressure values (≥130/85 mm of Hg), Serum Triglycerides (≥150 mg/dl), and Low-Density Lipoprotein (>130 mg/dl) were significantly elevated, and High-Density Lipoprotein (<40 mg/dl) was significantly low in LP than in controls (p < 0.05). Conclusion: The study showed a significant association of Metabolic Syndrome in patients with LP. Thus, patients with LP need to be screened to avoid complications associated with Metabolic Syndrome that is, Diabetes Mellitus, Cardiovascular Disease, colorectal cancer, and stroke.

Polyoxometalate-Guanosine Monophosphate Hydrogels with Haloperoxidase-like Activity for Antibacterial Performance.

Haloperoxidases represent an important class of enzymes that nature adopts as a defense mechanism to combat the colonial buildup of microorganisms on surfaces, commonly known as biofouling. Subsequently, there has been tremendous focus on the development of artificial haloperoxidase mimics that can catalyze the oxidation of X- (halide ion) in the presence of H2O2 to form HOX. The natural intermediate HOX disrupts the bacterial quorum sensing, thus preventing biofilm formation. Herein, we report a simple method for the formation of supramolecular hydrogels through the self-assembly of Keggin-structured polyoxometalates, phosphotungstic acid, and silicotungstic acid with the small biomolecule guanosine monophosphate (GMP) in an aqueous medium. The polyoxometalate-GMP hydrogels that contained highly entangled nanofibers were mechanically robust and showed thixotropic properties. The gelation of the polyoxometalates with GMP not only rendered manifold enhancement in biocompatibility but also the fibril network in the hydrogel provided high water wettability and the polyoxometalates acted as an efficient haloperoxidase mimic to trigger oxidative iodination, as demonstrated by a haloperoxidase assay. The antifouling activity of the phosphotungstic acid-GMP hydrogel was demonstrated against both Gram-positive and Gram-negative bacteria, which showed enhanced antibacterial performance of the hydrogel as compared to the polyoxometalate alone. We envision that the polyoxometalate-GMP hydrogels may facilitate mechanically robust coatings in a simple pathway that can be useful for antifouling applications.

Investigating Degradation Mechanisms in PtCo Alloy Catalysts: The Role of Co Content and a Pt-Rich Shell Using Operando High-Energy Resolution Fluorescence Detection X-ray Absorption Spectroscopy.

Low Pt-based alloy catalysts are regarded as an efficient strategy in achieving high activity for the oxygen reduction reaction (ORR) in proton-exchange membrane fuel cells (PEMFCs). However, the desired durability for the low Pt-based catalysts, such as the Pt1Co3 catalyst, has still been considered a great challenge for PEMFCs. In this study, we investigate sub-2.5 nm PtxCoy alloy catalysts with varying Co content and Pt1Co3@Pt core-shell (CS) nanostructure catalysts obtained through a simple displacement reaction. The Pt1Co3@Pt_H catalysts showed a high mass activity (MA) of 1.46 A/mgPt at 0.9 V and 14% MA loss after 10k accelerated degradation test (ADT) cycles, which suggested the improved stability compared with Pt1Co3 catalysts (52% MA loss). To clarify the degradation mechanism, operando high-energy resolution fluorescence detection X-ray absorption spectroscopy (XAS) was applied in addition to conventional advanced measurement techniques, including operando conventional XAS, to analyze the electronic state and structure changes during operation potentials. We found that introducing Co improves the catalysts' activity mainly from the strain effect, but an excessive amount of Co leads to increased Pt-oxidation, which accelerates the degradation of the catalysts. The Pt1Co3@Pt_H catalyst shows high tolerance to Pt-oxidation, benefiting both the stability and activity. Our findings demonstrate an in-depth understanding of the degradation mechanism and the importance of designing PtCo CS nanostructures with optimal Co content for enhanced performance in PEMFCs.

Improving the Cyclic Reversibility of Layered Li-Rich Cathodes by Combining Oxygen Vacancies and Surface Fluorination.

Layered-type Li-rich cathode materials have attracted significant attention for next-generation Li-ion batteries, but the advantage of their high capacity is eclipsed by their poor reversibility upon cycling. Irreversible oxygen redox activity and surface degradation have been deemed as the root cause and direct cause for their poor performance, respectively. We attempted to suppress surface degradation by inserting fluoride ions up to some depth on the surface. By fluorination with NH4HF2 after introducing a significant amount of oxygen vacancies in layered Li1.2Ni0.2Co0.2Mn0.4O2 by using CaH2 as a reducing agent, the reversible capacity reached 268 mAh/g, and the capacity retention after 100 cycles was about 99%. The scanning transmission electron microscopy-electron energy loss spectroscopy (STEM-EELS) technique revealed that, in contrast to directly fluorinated samples, our materials exhibit deeper fluorine signals besides surface signals, and hard X-ray photoelectron spectroscopy (HAXPES) patterns show ionic and covalent fluorine coordination. These results indicate that the combination of oxygen deficiency introduction and surface fluorination allows some F- ions to occupy near-surface oxygen vacancy sites rather than forming only a LiF layer on the surface, suggesting a new strategy to modify cathode materials for lithium-ion batteries.

Recurrent toxic epidermal necrolysis with two different drugs in a patient with chronic kidney disease-A case report with an atypical presentation.

Toxic epidermal necrolysis (TEN) is a dermatologic emergency usually attributed to drugs. Recurrent episodes of TEN are more common in the pediatric population than in adults. Patients carrying susceptible specific haplotypes, cross-reactivity between the drugs, and drug metabolites generated by the Cytochrome P450 are the key factors for the recurrent episodes. Chronic kidney disease (CKD) increases the risk of toxic epidermal necrolysis by altering the pharmacokinetics and pharmacodynamics of the drug with comparatively higher mortality in this group of patients. We hereby present an elderly female with 2 episodes of TEN following intake of furosemide at present and Nimesulide 3 years back. Cross-reactivity between these drugs because of the similar stereochemical structure might have triggered the second episode. The second episode of TEN was milder in presentation with a short latency period without any constitutional symptoms as compared to the first episode. Thus, treating physicians should always consider cross-reactivity between the chosen drugs in order to prevent subsequent life-threatening episodes, especially in patients with CKD.

Herpes zoster occurring over the site of tinea cruris-A case report based on the model of T-cell exhaustion in the Ruocco's immunocompromised cutaneous district.

Immunocompromised district refers to the area of the skin with altered immune response predisposing secondary diseases to develop in an immunocompetent individual. This might be explained by the theory of T-cell exhaustion which is characterized by the impairment of the effector function of antigen-specific T cells due to chronic persistence of the primary antigen. T-cell exhaustion model is not well known; however, it serves as a newer concept in the pathogenesis of diseases occurring simultaneously over the same site. Thus, it is not surprising to have two different infectious or non-infectious dermatoses over the same site one preceding the other as observed in our patient. The concept of immunocompromised district and T-cell exhaustion is a rare phenomenon; however, it should be identified by the treating physicians/dermatologists for the optimum management of the atypical presentation of the diseases.

New insights into molecular signaling pathways and current advancements in prostate cancer diagnostics & therapeutics.

Prostate adenocarcinoma accounts for more than 20% of deaths among males due to cancer. It is the fifth-leading cancer diagnosed in males across the globe. The mortality rate is quite high due to prostate cancer. Despite the fact that advancements in diagnostics and therapeutics have been made, there is a lack of effective drugs. Metabolic pathways are altered due to the triggering of androgen receptor (AR) signaling pathways, and elevated levels of dihydrotestosterone are produced due to defects in AR signaling that accelerate the growth of prostate cancer cells. Further, PI3K/AKT/mTOR pathways interact with AR signaling pathway and act as precursors to promote prostate cancer. Prostate cancer therapy has been classified into luminal A, luminal B, and basal subtypes. Therapeutic drugs inhibiting dihydrotestosterone and PI3K have shown to give promising results to combat prostate cancer. Many second-generation Androgen receptor signaling antagonists are given either as single agent or with the combination of other drugs. In order to develop a cure for metastasized prostate cancer cells, Androgen deprivation therapy (ADT) is applied by using surgical or chemical methods. In many cases, Prostatectomy or local radiotherapy are used to control metastasized prostate cancer. However, it has been observed that after 1.5 years to 2 years of Prostatectomy or castration, there is reoccurrence of prostate cancer and high incidence of castration resistant prostate cancer is seen in population undergone ADT. It has been observed that Androgen derivation therapy combined with drugs like abiraterone acetate or docetaxel improve overall survival rate in metastatic hormone sensitive prostate cancer (mHSPC) patients. Scientific investigations have revealed that drugs inhibiting poly ADP Ribose polymerase (PARP) are showing promising results in clinical trials in the prostate cancer population with mCRPC and DNA repair abnormalities. Recently, RISUG adv (reversible inhibition of sperm under guidance) has shown significant results against prostate cancer cell lines and MTT assay has validated substantial effects of this drug against PC3 cell lines. Current review paper highlights the advancements in prostate cancer therapeutics and new drug molecules against prostate cancer. It will provide detailed insights on the signaling pathways which need to be targeted to combat metastasized prostate cancer and castration resistant prostate cancer.

Genome-wide identification and gene expression analysis of GHMP kinase gene family in banana cv. Rasthali.

BACKGROUND: The GHMP kinase gene family encompasses ATP-dependent kinases, significantly involved in the biosynthesis of isoprenes, amino acids, and metabolism of carbohydrates. Banana is a staple tropical crop that is globally consumed but known for high sensitivity to salt, cold, and drought stresses. The GHMP kinases are known to play a significant role during abiotic stresses in plants. The present study emphasizes the role of GHMP kinases in various abiotic stress conditions in banana. METHODS AND RESULTS: We identified 12 GHMP kinase (MaGHMP kinase) genes in the banana genome database and witnessed the presence of the conserved Pro-X-X-X-Gly-Leu-X-Ser-Ser-Ala domain in their protein sequences. All genes were found to be involved in ATP-binding and carried kinase activity confronting their biological roles in the isoprene (27%) and amino acid (20%) biosyntheses. The expression analysis of genes during cold, drought, and salt stress conditions in tissue culture grown banana cultivar Rasthali plants showed a significant involvement of MaGHMP kinase genes in these stress conditions. The highest expression of MaGHMP kinase3 (8.5 fold) was noted during cold stress, while MaGHMP kinase1 (25 fold and 40.01 fold) showed maximum expression during drought and salt stress conditions in leaf tissue of Rasthali. CONCLUSION: Our findings suggested that MaGHMP kinase1 (MaHSK) and MaGHMP kinase3 (MaGlcAK) could be considered promising candidates for thwarting the abiotic stresses in banana.

Physico-chemical, sensory, and microbiological quality of raw chicken meat: an exploratory study in the Hisar city of Haryana, India.

A survey was conducted in Hisar, located in Haryana, India, to assess the quality of raw chicken meat. To ensure comprehensive coverage, healthy broiler chickens were obtained from various meat retail outlets in Hisar city, encompassing the majority of such establishments. Additionally, a sample of control chickens was obtained from the Livestock Farm, College of Veterinary Sciences, Lala Lajpat Rai University of Veterinary and Animal Sciences (LUVAS), Hisar, Haryana, India. The raw chicken meat was grouped into two categories, breast cut and thigh cut. The breast muscles, which include pectoralis major and pectoralis minor, and the thigh muscles, which include the abductor muscles, were chosen as the samples for proximate analysis, which included physico-chemical, sensory, and microbiological analyses of raw chicken meat. The analysis of the raw meat in the laboratory revealed inconsistent variations between the control and retail samples in terms of parameters, such as proximate composition, pH, the water-holding capacity (WHC), thiobarbituric acid (TBA), instrumental color analysis, and sensory evaluation. The moisture content of the control breast sample was significantly higher (p < 0.05) than that of the samples from shops 2, 3, and 5. However, it was statistically similar to that of the samples from shops 1, 4, and 6. The total plate and psychrotrophic counts of the control thigh sample were significantly lower than those of the samples from shops 3, 4, 5, and 6. Among the thigh pH values, the samples from shops 1, 2, 5, and 6 had significantly higher pH values than the control sample. The variations in the various parameters were multifactorial and established the superiority of birds slaughtered under laboratory conditions and grown in university farms compared to the raw chicken meat available in retail outlets in Hisar city.

Utility of C3d and C4d immunohistochemical staining in formalin-fixed skin or mucosal biopsy specimens in diagnosis of bullous pemphigoid and mucous membrane pemphigoid.

Bullous pemphigoid (BP) and mucous membrane pemphigoid (MMP) sometimes have overlapping clinical, histopathological, and direct immunofluorescence (DIF) features in the early stages. Complement deposition is an intrinsic component of the patho-mechanism of BP in contrast to MMP. Hence immunohistochemistry (IHC) for C3d and C4d may be helpful in differentiating the two disorders. Seventy-four patients of BP and 18 patients of MMP along with 10 negative controls were enrolled in this study. C3d and C4d IHC was performed in formalin-fixed skin biopsy specimens. C3d IHC staining in BP/MMP had a sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 59.2%/41.2%, 100%/100%, 100%/100%, 25.6%/50.0%, respectively. C4d IHC staining in BP/MMP had a sensitivity, specificity, PPV and NPV of 26.8%/17.6%, 100%/100%, 100%/100% and 16.1%/41.7%, respectively. Receiver operator analysis showed utility of C3d in diagnosing both BP [Area under curve (AUC) = 0.8, p = 0.0001] and MMP (AUC = 0.71; p = 0.001). C4d was useful in diagnosis of BP (AUC = 0.5; p = 0.0001), but not MMP (AUC = 0.6; p = 0.064). Hence, C3d is a better diagnostic modality for BP as compared to C4d, whereas C3d and C4d have lower diagnostic importance in MMP. C3d IHC can be employed in diagnosing BP when a second biopsy for direct immunofluorescence (DIF) is not possible or where a facility for IF microscopy does not exist.