A Comprehensive Review and Androgen Deprivation Therapy and Its Impact on Alzheimer's Disease Risk in Older Men with Prostate Cancer.

Prostate cancer (PCa) is one of the most prevalent malignancies affecting males worldwide. Despite reductions in mortality rates due to advances in early identification and treatment methods, PCa remains a major health concern. Recent research has shed light on a possible link between PCa and Alzheimer's disease (AD), which is a significant neurological ailment that affects older males all over the world. Androgen deprivation therapy (ADT), a cornerstone therapeutic method used in conjunction with radiation and palliative care in advanced metastatic PCa cases, is critical for disease management. Evidence reveals a relationship between ADT and cognitive impairment. Hormonal manipulation may cause long-term cognitive problems through processes such as amyloid beta (Aß) aggregation and neurofibrillary tangles (NFTs). Fluctuations in basal androgen levels can upset the delicate balance of genes that are sensitive to androgen levels, contributing to cognitive impairment. This detailed review dives into the various aspects of PCa aetiology and its relationship with cognitive decline. It investigates the discovery of particular biomarkers, as well as microRNAs (miRNAs), which play important roles in pathogenic progression. The review attempts to identify potential biomarkers associated with ADT-induced cerebral changes, including Aß oligomer buildup, NFT formation, and tauopathy, which can contribute to early-onset dementia and cognitive impairment. Besides it further aims to provide insights into innovative diagnostic and therapeutic avenues for alleviating PCa and ADT-related cognitive sequelae by unravelling these complicated pathways and molecular mechanisms.

Review of Pharmacotherapeutic Targets in Alzheimer's Disease and Its Management Using Traditional Medicinal Plants.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and impaired daily functioning. While there is currently no cure for AD, several pharmacotherapeutic targets and management strategies have been explored. Additionally, traditional medicinal plants have gained attention for their potential role in AD management. Pharmacotherapeutic targets in AD include amyloid-beta (Aß) aggregation, tau protein hyperphosphorylation, neuroinflammation, oxidative stress, and cholinergic dysfunction. Traditional medicinal plants, such as Ginkgo biloba, Huperzia serrata, Curcuma longa (turmeric), and Panax ginseng, have demonstrated the ability to modulate these targets through their bioactive compounds. Ginkgo biloba, for instance, contains flavonoids and terpenoids that exhibit neuroprotective effects by reducing Aß deposition and enhancing cerebral blood flow. Huperzia serrata, a natural source of huperzine A, has acetylcholinesterase-inhibiting properties, thus improving cholinergic function. Curcuma longa, enriched with curcumin, exhibits anti-inflammatory and antioxidant effects, potentially mitigating neuroinflammation and oxidative stress. Panax ginseng's ginsenosides have shown neuroprotective and anti-amyloidogenic properties. The investigation of traditional medicinal plants as a complementary approach to AD management offers several advantages, including a lower risk of adverse effects and potential multi-target interactions. Furthermore, the cultural knowledge and utilization of these plants provide a rich source of information for the development of new therapies. However, further research is necessary to elucidate the precise mechanisms of action, standardize preparations, and assess the safety and efficacy of these natural remedies. Integrating traditional medicinal-plant-based therapies with modern pharmacotherapies may hold the key to a more comprehensive and effective approach to AD treatment. This review aims to explore the pharmacotherapeutic targets in AD and assess the potential of traditional medicinal plants in its management.

Toxic heavy metal ions contamination in water and their sustainable reduction by eco-friendly methods: isotherms, thermodynamics and kinetics study.

Heavy metal ions can be introduced into the water through several point and non-point sources including leather industry, coal mining, agriculture activity and domestic waste. Regrettably, these toxic heavy metals may pose a threat to both humans and animals, particularly when they infiltrate water and soil. Heavy metal poisoning can lead to many health complications, such as liver and renal dysfunction, dermatological difficulties, and potentially even malignancies. To mitigate the risk of heavy metal ion exposure to humans and animals, it is imperative to extract them from places that have been polluted. Several conventional methods such as ion exchange, reverse osmosis, ultrafiltration, membrane filtration and chemical precipitation have been used for the removal of heavy metal ions. However, these methods have high operation costs and generate secondary pollutants during water treatment. Biosorption is an alternative approach to eliminating heavy metals from water that involves employing eco-friendly and cost-effective biomass. This review is focused on the heavy metal ions contamination in the water, biosorption methods for heavy metal removal and mathematical modeling to explain the behaviour of heavy metal adsorption. This review can be helpful to the researchers to design wastewater treatment plants for sustainable wastewater treatment.

Current perspective in research and industrial applications of microbial cellulases.

The natural interactions between various bacteria, fungi, and other cellulolytic microorganisms destroy lignocellulosic polymers. The efficacy of this process is determined by the combined action of three main enzymes: endoglucanases, exo-glucanases, and ß-glucosidase. The enzyme attacks the polymeric structure's ß-1,4-linkages during the cellulose breakdown reaction. This mechanism is crucial for the environment as it recycles cellulose in the biosphere. However, there are problems with enzymatic cellulose breakdown, including complex cellulase structure, insufficient degradation efficacy, high production costs, and post-translational alterations, many of which are closely related to certain unidentified cellulase properties. These issues impede the practical use of cellulases. A developing area of research is the application of this similar paradigm for industrial objectives. Cellulase enzyme exhibits greater promise in many critical industries, including biofuel manufacture, textile smoothing and finishing, paper and pulp manufacturing, and farming. However, the study on cellulolytic enzymes must move forward in various directions, including increasing the activity of cellulase as well as designing peptides to give biocatalysts their desired attributes. This manuscript includes an overview of current research on different sources of cellulases, their production, and biochemical characterization.

Arsenic exposure to mouse visceral leishmaniasis model through their drinking water linked to the disease exacerbation via modulation in host protective immunity: a preclinical study.

A large body of evidence has shown a direct link between arsenic exposure and drug resistance to Leishmania parasites against antimonial preparations in visceral leishmaniasis (VL) hyper-endemic regions, especially in India and its sub-continent. However, the implicated roles of arsenic on the VL host, pathophysiological changes, and immune function have not yet been clarified, particularly at the reported concentration of arsenic in the VL hyper-endemic area of Bihar, India. Herein, we exposed the mouse VL model to arsenic (0.5 mg/L to 2 mg/L) through their drinking water and analyzed its effect on T cells proliferation, Th1/Th2-mediators, MAPK signaling cascade, and parasite load in preclinical models. Coherently, the parasite count in Giemsa stained spleen imprint has been investigated and found significant positive associations with levels of arsenic exposure. The liver and kidney function tests (AST, ALT, ALP, BUN, Creatinine, Urea, etc.) are apparent to hepatonephric toxicity in arsenic exposed VL mice compared to unexposed. This observation appears to be consistent with the up-regulated expression of immune regulatory Th2 mediators (IL-4, IL-10, TGF-ß) and down-regulated expression of Th1 mediators (IL-12, IFN-γ, TNF-α) with a suppressed leishmanicidal function of macrophage (ROS, NO, iNOS). We also established that arsenic exposure modulated the host ERK-1/2 and p38 MAPK signaling cascade, limited T lymphocyte proliferation, and a lower IgG2a/IgG1 ratio to favor the Leishmania parasite survival inside the host. This study suggests that the contorted Th1-subtype and exacerbated Th2-subtype immune responses are involved in the increased susceptibility and pathogenesis of Leishmania parasite among subjects/individuals regularly exposed to arsenic.

Combined use of hair follicle stem cells and CEPO (carbamylated erythropoietin)-Fc in a rat model of chronic cerebral hypoperfusion: A behavioral, electrophysiological, and molecular study.

BACKGROUND: In dementia, synaptic dysfunction appears before neuronal loss. Stem cell therapy could potentially provide a promising strategy for the treatment of dementia models. The carbamylated erythropoietin fusion protein (CEPO-Fc) has shown synaptotrophic effects. This study aimed to determine the efficiency of the combined use of hair follicle stem cells (HFSC) and CEPO-Fc in the basal synaptic transmission (BST) and long-term plasticity (LTP) of chronic cerebral hypoperfusion (CCH) rats. METHODS: We divided 64 adult rats into control, sham, CCH+vehicle, CCH+CEPO, CCH+HFSC, and CCH+HFSC+CEPO groups. The CEPO-Fc was injected three times/week for 30 days. HFSC transplantation was done on days 4, 14, and 21 after surgery. The Morris water maze test and passive avoidance were used to assess memory. BST and LTP were assessed by a field-potential recording of the CA1 region. The hippocampal mRNA expression of IGF-1, TGF-ß1, ß1-Catenine, NR2B, PSD-95, and GSk-3ß was evaluated by quantitative RT-PCR. RESULTS: Following combination therapy, spatial memory retention, and BST showed significant improvement relative to HFSC and CEPO-Fc groups. These effects were also confirmed by recovered mRNA expression of ß1-catenin, TGF-ß1, and NR2B. GSK-3ß expression was downregulated in all treatment groups. The upregulated PSD-95 was identified in HFSC and combination groups compared to the vehicle group. CONCLUSIONS: These findings indicate that the combined use of HFSC and CEPO-Fc may be more advantageous for treating memory disruption in the CCH model than CEPO-Fc or HFSC alone. This type of combination therapy may hopefully lead to a new approach to treatment for dementia.

In Silico Insight to Identify Potential Inhibitors of BUB1B from Mushroom Bioactive Compounds to Prevent Breast Cancer Metastasis.

BACKGROUND: Breast cancer is one of the most common types of cancer among women worldwide, and its metastasis is a significant cause of mortality. Therefore, identifying potential inhibitors of proteins involved in breast cancer metastasis is crucial for developing effective therapies. BUB1 mitotic checkpoint serine/threonine kinase B (BUB1B) is a key regulator of mitotic checkpoint control, which ensures the proper segregation of chromosomes during cell division. Dysregulation of BUB1B has been linked to a variety of human diseases, including breast cancer. Overexpression of BUB1B has been observed in various cancer types, and its inhibition has been shown to induce cancer cell death. Additionally, BUB1B inhibition has been suggested as a potential strategy for overcoming resistance to chemotherapy and radiation therapy. Given the importance of BUB1B in regulating cell division and its potential as a therapeutic target, the development of BUB1B inhibitors has been the focus of intense research efforts. Despite these efforts, few small molecule inhibitors of BUB1B have been identified, highlighting the need for further research in this area. In this study, the authors aimed to identify potential inhibitors of BUB1B from mushroom bioactive compounds using computational methods, which could ultimately lead to the development of new treatments for breast cancer metastasis. METHODS: This study has incorporated 70 bioactive compounds (handpicked through literature mining) of distinct mushrooms that were considered and explored to identify a suitable drug candidate. Their absorption, distribution, metabolism and excretion (ADME) properties were obtained to predict the drug-likeness of these 70 mushroom compounds based on Lipinski's rule of 5 (RO5). Screening these bioactive compounds and subsequent molecular docking against BUB1B provided compounds with the best conformation-based binding affinity. The best two complexes, i.e., BUB1B-lepitaprocerin D and BUB1B-peptidoglycan, were subjected to molecular dynamic simulations. Both complexes were assessed for their affinity, stability, and flexibility in protein-ligand complex systems. RESULTS: The molecular dynamic (MD) simulation studies revealed that lepitaprocerin D has an energetically favorable binding affinity with BUB1B. Results showed that the formation of a hydrogen bond between residues ASN123 and SER157, and lepitaprocerin D had strengthened the affinity of lepitaprocerin D with BUB1B. CONCLUSIONS: This study identified lepitaprocerin D as a potential and novel inhibitor for BUB1B that could be a plausible drug candidate for identifying and controlling the spread of breast cancer metastasis.

WNT-ß Catenin Signaling as a Potential Therapeutic Target for Neurodegenerative Diseases: Current Status and Future Perspective.

Wnt/ß-catenin (WßC) signaling pathway is an important signaling pathway for the maintenance of cellular homeostasis from the embryonic developmental stages to adulthood. The canonical pathway of WßC signaling is essential for neurogenesis, cell proliferation, and neurogenesis, whereas the noncanonical pathway (WNT/Ca2+ and WNT/PCP) is responsible for cell polarity, calcium maintenance, and cell migration. Abnormal regulation of WßC signaling is involved in the pathogenesis of several neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and spinal muscular atrophy (SMA). Hence, the alteration of WßC signaling is considered a potential therapeutic target for the treatment of neurodegenerative disease. In the present review, we have used the bibliographical information from PubMed, Google Scholar, and Scopus to address the current prospects of WßC signaling role in the abovementioned neurodegenerative diseases.

Evaluation of Pleurotus Mushroom Effects on Histopathological Changes in Organs of Diabetic Rats.

Diabetes mellitus (DM) is a metabolic disorder that can be categorized mainly into type 1 and type 2. Diabetes type 1 is caused due to ß-cell destruction, whereas type 2 is caused by the resistance of cell receptors. Many therapies are available for the management of diabetes, but they have some side effects, and as a result of this, people are attracted to natural treatments. Pleurotus mushrooms are well documented for their medicinal attributes and their role in the treatment of diseases like cancer, infectious disease, neurodiseases, and inflammatory disease. The protective mechanism of the Pleurotus fossulatus (P. fossulatus) mushroom and its detailed histological study on kidneys and the liver in diabetic conditions were unexplored. The present study evaluated the effects of P. fossulatus aqueous extract on histological changes in the diabetic rat model. Male Wistar albino rats were used to create the diabetic model by using streptozotocin (STZ) intraperitoneal (IP) injection. The animals were separated into five different groups, with six animals in each. Only group I, animals that did not receive STZ, was considered a normal control. Group II was a diabetic control and received normal saline, and group III was a drug control and received metformin as a standard drug. Groups IV and V were dosing groups, which received the aqueous extract of P. fossulatus in 250 mg/kg and 500 mg/kg of body weight concentrations, labeled as T1 and T2 groups, respectively. The T1 and T2 groups clearly showed their potential to reverse the histopathological changes in the kidney and liver. However, the T2 group was more effective than the T1 group, as results indicate that functions of the glomerulus and its structural deformity were restored to their near-natural form in the T2 group. In the case of the liver, the histological changes like the dilatation of sinusoids, more numbers of the Kupffer cell formation, and necrosis were restored in the T2 group. All these results proved the potential of P. fossulatus against the side effects of diabetes. It could protect the organs from developing diabetic nephropathy (DN) and liver-related diseases like cirrhosis and nonalcoholic fatty liver disease (NAFLD).

Biosynthesis and Bioapplications of Nanomaterials from Mushroom Products.

The production of nanoparticles (NPs) from chemical and physical synthesis has ended due to the involvement of toxic byproducts and harsh analytical conditions. Innovation and research in nanoparticle synthesis are derived from biomaterials that have gained attention due to their novel features, such as ease of synthesis, low-cost, eco-friendly approach, and high water solubility. Nanoparticles obtained through macrofungi involve several mushroom species, i.e., Pleurotus spp., Ganoderma spp., Lentinus spp., and Agaricus bisporus. It is well-known that macrofungi possess high nutritional, antimicrobial, anti-cancerous, and immune-modulatory properties. Nanoparticle synthesis via medicinal and edible mushrooms is a striking research field, as macrofungi act as an eco-friendly biofilm that secretes essential enzymes to reduce metal ions. The mushroom-isolated nanoparticles exhibit longer shelf life, higher stability, and increased biological activities. The synthesis mechanisms are still unknown; evidence suggests that fungal flavones and reductases have a significant role. Several macrofungi have been utilized for metal synthesis (such as Ag, Au, Pt, Fe) and non-metal nanoparticles (Cd, Se, etc.). These nanoparticles have found significant applications in advancing industrial and bio-medical ventures. A complete understanding of the synthesis mechanism will help optimize the synthesis protocols and control the shape and size of nanoparticles. This review highlights various aspects of NP production via mushrooms, including its synthesis from mycelium and the fruiting body of macrofungi. Also, we discuss the applications of different technologies in NP high-scale production via mushrooms.

Identification of Prognostic Biomarkers for Suppressing Tumorigenesis and Metastasis of Hepatocellular Carcinoma through Transcriptome Analysis.

Cancer is one of the deadliest diseases developed through tumorigenesis and could be fatal if it reaches the metastatic phase. The novelty of the present investigation is to explore the prognostic biomarkers in hepatocellular carcinoma (HCC) that could develop glioblastoma multiforme (GBM) due to metastasis. The analysis was conducted using RNA-seq datasets for both HCC (PRJNA494560 and PRJNA347513) and GBM (PRJNA494560 and PRJNA414787) from Gene Expression Omnibus (GEO). This study identified 13 hub genes found to be overexpressed in both GBM and HCC. A promoter methylation study showed these genes to be hypomethylated. Validation through genetic alteration and missense mutations resulted in chromosomal instability, leading to improper chromosome segregation, causing aneuploidy. A 13-gene predictive model was obtained and validated using a KM plot. These hub genes could be prognostic biomarkers and potential therapeutic targets, inhibition of which could suppress tumorigenesis and metastasis.

Heavy Metal Contamination in the Aquatic Ecosystem: Toxicity and Its Remediation Using Eco-Friendly Approaches.

Urbanization and industrialization are responsible for environmental contamination in the air, water, and soil. These activities also generate large amounts of heavy metal ions in the environment, and these contaminants cause various types of health issues in humans and other animals. Hexavalent chromium, lead, and cadmium are toxic heavy metal ions that come into the environment through several industrial processes, such as tanning, electroplating, coal mining, agricultural activities, the steel industry, and chrome plating. Several physical and chemical methods are generally used for the heavy metal decontamination of wastewater. These methods have some disadvantages, including the generation of secondary toxic sludge and high operational costs. Hence, there is a need to develop a cost-effective and eco-friendly method for the removal of heavy metal ions from polluted areas. Biological methods are generally considered eco-friendly and cost-effective. This review focuses on heavy metal contamination, its toxicity, and eco-friendly approaches for the removal of heavy metals from contaminated sites.

Inter and intracellular mitochondrial transfer: Future of mitochondrial transplant therapy in Parkinson's disease.

Parkinson's disease (PD) is marked by the gradual degeneration of dopaminergic neurons and the intracellular build-up of Lewy bodies rich in α-synuclein protein. This impairs various aspects of the mitochondria including the generation of ROS, biogenesis, dynamics, mitophagy etc. Mitochondrial dynamics are regulated through the inter and intracellular movement which impairs mitochondrial trafficking within and between cells. This inter and intracellular mitochondrial movement plays a significant role in maintaining neuronal dynamics in terms of energy and growth. Kinesin, dynein, myosin, Mitochondrial rho GTPase (Miro), and TRAK facilitate the retrograde and anterograde movement of mitochondria. Enzymes such as Kinases along with Calcium (Ca2+), Adenosine triphosphate (ATP) and the genes PINK1 and Parkin are also involved. Extracellular vesicles, gap junctions, and tunneling nanotubes control intercellular movement. The knowledge and understanding of these proteins, enzymes, molecules, and movements have led to the development of mitochondrial transplant as a therapeutic approach for various disorders involving mitochondrial dysfunction such as stroke, ischemia and PD. A better understanding of these pathways plays a crucial role in establishing extracellular mitochondrial transplant therapy for reverting the pathology of PD. Currently, techniques such as mitochondrial coculture, mitopunch and mitoception are being utilized in the pre-clinical stages and should be further explored for translational value. This review highlights how intercellular and intracellular mitochondrial dynamics are affected during mitochondrial dysfunction in PD. The field of mitochondrial transplant therapy in PD is underlined in particular due to recent developments and the potential that it holds in the near future.

Simultaneous removal of ternary heavy metal ions by a newly isolated Microbacterium paraoxydans strain VSVM IIT(BHU) from coal washery effluent.

In the present work, the removal of Cr (VI), Cd (II) and Pb (II) at 50 mg/L of each metal ion concentration was investigated by Microbacterium paraoxydans strain VSVM IIT(BHU). The heavy metal binding on the bacterial cell surface was confirmed through X-ray photoelectron spectroscopy and energy dispersive X-ray. X-ray photoelectron spectroscopy analysis also confirmed the reduction of Cr (VI) to Cr (III). Heavy metal removal dynamics was investigated by evaluating dimensionless, and the value of Nk (9.49 × 10-3, 9.92 × 10-3 and 1.23 × 10-2 for Cr (VI), Cd (II) and Pb (II) ions) indicated that the removal of heavy metals by bacterial isolate was mixed diffusion and transfer controlled. It was found that both the experimental and predicted values for isolated bacterial strain coincided with each other with a good R2 value in the L-M Algorithm range of 0.94-0.98 for the ternary metal ion system. The bacterial isolate presented a maximum heavy metal ion removal efficiency of 91.62% Cr (VI), 89.29% Pb (II), and 83.29% Cd (II) at 50 mg/L.

Hexavalent-Chromium-Induced Oxidative Stress and the Protective Role of Antioxidants against Cellular Toxicity.

Hexavalent chromium is a highly soluble environmental contaminant. It is a widespread anthropogenic chromium species that is 100 times more toxic than trivalent chromium. Leather, chrome plating, coal mining and paint industries are the major sources of hexavalent chromium in water. Hexavalent chromium is widely recognised as a carcinogen and mutagen in humans and other animals. It is also responsible for multiorgan damage, such as kidney damage, liver failure, heart failure, skin disease and lung dysfunction. The fate of the toxicity of hexavalent chromium depends on its oxidation state. The reduction of Cr (VI) to Cr (III) is responsible for the generation of reactive oxygen species (ROS) and chromium intermediate species, such as Cr (V) and Cr (IV). Reactive oxygen species (ROS) are responsible for oxidative tissue damage and the disruption of cell organelles, such as mitochondria, DNA, RNA and protein molecules. Cr (VI)-induced oxidative stress can be neutralised by the antioxidant system in human and animal cells. In this review, the authors summarise the Cr (VI) source, toxicity and antioxidant defence mechanism against Cr (VI)-induced reactive oxygen species (ROS).

Metagenomic Analysis of Garden Soil-Derived Microbial Consortia and Unveiling Their Metabolic Potential in Mitigating Toxic Hexavalent Chromium.

Soil microbial communities connect to the functional environment and play an important role in the biogeochemical cycle and waste degradation. The current study evaluated the distribution of the core microbial population of garden soil in the Varanasi region of Uttar Pradesh, India and their metabolic potential for mitigating toxic hexavalent chromium from wastewater. Metagenomes contain 0.2 million reads and 56.5% GC content. The metagenomic analysis provided insight into the relative abundance of soil microbial communities and revealed the domination of around 200 bacterial species belonging to different phyla and four archaeal phyla. The top 10 abundant genera in garden soil were Gemmata, Planctomyces, Steroidobacter, Pirellula, Pedomicrobium, Rhodoplanes, Nitrospira Mycobacterium, Pseudonocardia, and Acinetobacter. In this study, Gemmata was dominating bacterial genera. Euryarchaeota, Parvarchaeota, and Crenarchaeota archaeal species were present with low abundance in soil samples. X-ray photoelectric spectroscopy (XPS) analysis indicates the presence of carbon, nitrogen-oxygen, calcium, phosphorous, and silica in the soil. Soil-derived bacterial consortia showed high hexavalent chromium [Cr (VI)] removal efficiency (99.37%). The bacterial consortia isolated from garden soil had an important role in the hexavalent chromium bioremediation, and thus, this study could be beneficial for the design of a heavy-metal treatment system.

Deciphering the gut microbiome in neurodegenerative diseases and metagenomic approaches for characterization of gut microbes.

The central nervous system has essential role in the regulation of the physiological condition of the human body. Gut microbes cause several types of gastrointestinal diseases like ulcer stomach and intestine and irritable bowel syndrome. Microbes present in the human gut can affect brain function by the release of neuroactive metabolites such as neurotransmitters, hormones, and other compounds. Gut microbial-derived metabolites also have an important role in neurological diseases such as Alzheimer's disease, Parkinson's disease, etc. Vital communication between the gut microbes and the central nervous system is known as the microbiota-gut-brain axis. It provides a communication pathway between the gut and brain which is made up of the vagus nerve, immune system components, and neuroendocrine. Disturbance in gut microbiota composition can alter the central nervous system and enteric nervous system functions. Metagenomics has been employed for the identification, and characterization of gut microbes and microbial-derived metabolites. This review is focused on the gut microbes-brain relationship and the role of gut microbes in neurodegenerative diseases. This study is also focused on major metagenomic approaches and their role in gut microbes characterization.

Exploring the Paradox of COVID-19 in Neurological Complications with Emphasis on Parkinson's and Alzheimer's Disease.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a human coronavirus (HCoV) that has created a pandemic situation worldwide as COVID-19. This virus can invade human cells via angiotensin-converting enzyme 2 (ACE2) receptor-based mechanisms, affecting the human respiratory tract. However, several reports of neurological symptoms suggest a neuroinvasive development of coronavirus. SARS-CoV-2 can damage the brain via several routes, along with direct neural cell infection with the coronavirus. The chronic inflammatory reactions surge the brain with proinflammatory elements, damaging the neural cells, causing brain ischemia associated with other health issues. SARS-CoV-2 exhibited neuropsychiatric and neurological manifestations, including cognitive impairment, depression, dizziness, delirium, and disturbed sleep. These symptoms show nervous tissue damage that enhances the occurrence of neurodegenerative disorders and aids dementia. SARS-CoV-2 has been seen in brain necropsy and isolated from the cerebrospinal fluid of COVID-19 patients. The associated inflammatory reaction in some COVID-19 patients has increased proinflammatory cytokines, which have been investigated as a prognostic factor. Therefore, the immunogenic changes observed in Parkinson's and Alzheimer's patients include their pathogenetic role. Inflammatory events have been an important pathophysiological feature of neurodegenerative diseases (NDs) such as Parkinson's and Alzheimer's. The neuroinflammation observed in AD has exacerbated the Aß burden and tau hyperphosphorylation. The resident microglia and other immune cells are responsible for the enhanced burden of Aß and subsequently mediate tau phosphorylation and ultimately disease progression. Similarly, neuroinflammation also plays a key role in the progression of PD. Several studies have demonstrated an interplay between neuroinflammation and pathogenic mechanisms of PD. The dynamic proinflammation stage guides the accumulation of α-synuclein and neurodegenerative progression. Besides, few viruses may have a role as stimulators and generate a cross-autoimmune response for α-synuclein. Hence, neurological complications in patients suffering from COVID-19 cannot be ruled out. In this review article, our primary focus is on discussing the neuroinvasive effect of the SARS-CoV-2 virus, its impact on the blood-brain barrier, and ultimately its impact on the people affected with neurodegenerative disorders such as Parkinson's and Alzheimer's.

Diagnosis of Genital Tuberculosis in Infertile Women by Using the Composite Reference Standard.

Female genital tuberculosis (FGTB) can be asymptomatic or even masquerade as other gynecological conditions. Conventional methods of FGTB diagnosis include various imaging, bacteriological, molecular, and pathological techniques that are only positive in a small percentage of patients, leaving many cases with undiagnosed condition. In the absence of a perfect diagnostic method, composite reference standards (CRSs) have been advocated in this diagnostic study. This study assesses the agreement between traditional diagnostic modalities using CRS and prevalent TB groups among different fallopian tube infertility manifestations. A total of 86 women with primary and secondary infertility were included in the study and subjected to bacteriological, pathological, and radiological examination for the diagnosis of FGTB. Results were evaluated statistically for concordance of the diagnostic tests to the CRS by sensitivity and specificity, while PPV and NPV were calculated for the performance of diagnostic tests of FGTB. We observed that 11.2% of women were found to be true positives by means of CRS. The positive findings by CRS were as follows: ultrasonography (13.9%), laparoscopy (14%), hysteroscopy (12%), GeneXpert (4.8%), culture (4.8%), polymerase chain reaction (4.8%), and histopathology (6.4%). GeneXpert and culture were found to have a perfect agreement with CRS. Hysterosalpingography, laparoscopy, and hysteroscopy have a fair agreement with CRS. Out of 43 women with tubal factor infertility, 6 women were found in the definitive TB group with mixed conditions of tubal manifestations. This study evaluates and demonstrates the reliability of the collective assessment of various diagnostic methods with CRS findings that help in identifying different TB groups of genital tuberculosis patients from all infertile patients by applying the criteria of CRS.