Allergy & Immunology
In silico Approaches for Investigation of the Natural Therapeutic Agents for Human Papillomavirus: Computer-aided Drug Design Perspective
Human papillomavirus infection a prevalent global sexually transmitted disease is linked to various malignancies like cervical cancer head-and-neck squamous cell carcinoma and anal cancer. Researchers are actively exploring phytoconstituents from medicinal plants.
This in silico study aims to assess the anti-human papillomavirus capabilities of phytochemical compounds sourced from Ocimum sanctum Curcuma longa Nyctanthes arbor-tristis Zingiber officinale Andrographis paniculata Acacia nilotica Psidium guajava Ficus religiosa Emblica officinalis and Tinospora cordifolia plants.
Through in silico studies the anti-human papillomavirus capabilities of these compounds were assessed focusing on their binding affinity to viral E6 protein. Phytochemicals absorption distribution metabolism excretion and toxicity (ADMET) analysis gauged drug-likeness and toxicity.
Notably compounds like Tinosporaside β-sitosterol β-sitosteryl-D-glucoside botulin ∞-amyrin and ß-amyrin exhibited strong binding affinity.
These findings provide insights for drug design encouraging further in-vitro and in-vivo analyses.
Antibacterial Activity of Medicinal Plants and the Impact of Isolated Bioactive Compounds against Methicillin Resistant Staphylococcus aureus
Staphylococcus aureus is amongst those microorganisms that have the ability to cause broad-spectrum infections. The bacteria can be both hospital and community-acquired due to the resistance mechanism developed against the available antibiotics. As the bacteria is resistant to almost all β-lactam antibiotic family its treatment is becoming increasingly difficult. Therefore new strategies should be implemented to control the pathogen which is fast transforming as a multi-drug resistant (MDR) microorganism. Medicinal plants serve as an alternative candidate to antibiotics due to the medicated efficacy attracting many researchers in the last decade. Several studies are being carried out worldwide to treat this pathogenic bacterium with the active ingredients present in various plant species. This review paper aims to depict the antibacterial activity of different medicinal plants and the impact of the isolated bioactive compounds against the multi-drug resistant (MDR) pathogen-methicillin-resistant Staphylococcus aureus (MRSA) and to introspect the mechanism of action of the natural products in interrupting the resistance mechanism of MRSA thereby killing the bacteria.
Chemical Identification of Purified Molecule (3-ethyl-6,7-dihydroxy-2-phenyl-chromen-4-one) Prepared from Alpinia officinarum with Anti-Cryptococcus neoformans Potential
Plants contain a large number of molecules with various potentials including antifungal impact. Cryptococcus neoformans (C. neoformans) is a yeast that causes Cryptococcosis infection in both immunocompromised and normal individuals worldwide.
This study aimed to investigate the inhibitory impact of plant extracts on C. neoformans and perform purification of the most bioactive product for further chemical identification.
The anti-C. neoformans potential of fourteen plants extracted by using various solvents including water methanol and benzene was tested. The most promising compound with anti-C. neoformans was purified. The minimal inhibitory level of the purified sub-fraction as compared to fluconazole as a standard drug was determined. The chemical identification of the purified product was carried out using FTIR 1HNMR elemental analysis and Mass spectroscopy.
Alpinia officinarum (A. officinarum) methanolic extract has the highest antifungal impact on C. neoformans and showed an inhibition zone of 3.2±0.2 cm. The methanolic extract was separated into 14 fractions where the fifth fraction showed the highest activity. It was further separated into four sub-fractions that were tested to characterize the most promising molecule with anti-C. neoformans impact which was further chemically identified as 3-Ethyl-67-dihydroxy-2-phenyl-chromen-4-one. The purified product led to significant alterations in the ultra-structure of C. neoformans relative to the standard drug.
A. officinarum contains 3-ethyl 67-dihydroxy-2-chromen-4-one as a promising molecule with anti-C. neoformans potential.
Synthesis, Computational Studies, and Biological Evaluation of Sulphamethoxazole-based Schiff Bases as Antimicrobial Agents
Sulphamethoxazole-based Schiff-base compounds display potential antibacterial and antifungal activity. Sulphamethoxazole is considered to be a versatile pharmacophore that can be utilized for designing and developing numerous bioactive lead compounds. In this work some new sulphamethoxazole-based Schiff base compounds were synthesized which are expected to possess antimicrobial activity making them potentially useful for treating microbial infections.
Concerning issues of drug resistance in presently available drugs this study aimed to synthesize new sulphamethoxazole-based Schiff bases and evaluate their antimicrobial activity.
New sulphamethoxazole-based Schiff bases were synthesized by condensing sulphamethoxazole with various acetophenones in methanol in the presence of glacial acetic acid. The synthesized compounds were characterized using various techniques such as TLC melting point IR NMR and mass analysis. The computational properties of the compounds were also assessed using online software programs and the similarity of the target compounds was also calculated as compared to sulphamethoxazole and clotrimazole. The antimicrobial activity of the target compounds was tested against Bacillus subtilis (Gram-positive) Escherichia coli (Gram-negative) and Candida albicans.
The target compounds (3a-f) were successfully synthesized and characterized by spectroscopic and analytical methods. The results of computational properties similarity and antimicrobial activity against B. subtilis E. coli and C. albicans of new sulphamethoxazole-based Schiff bases showed significant antimicrobial potential.
The synthesized new Schiff bases particularly compound 3c exhibited promising antimicrobial activity and good physicochemical properties as compared to standard drugs indicating their potential for further development as antimicrobial agents.
Synthesis, Characterization, and Anticancer, Antidiabetic, and Antimicrobial Activities of Azo-Schiff Base Ligand with ONO Donor Atom and its Transition Metal Complexes
Cancer diabetes and infection of bacteria and fungi are serious issues in the world. Synthesis of the potential drugs against them is a major challenge to the researcher. Hence coordination chemistry has attracted researchers as it has various applications in medicinal and biological fields.
Synthesis and biological evolution of azo-Schiff base ligand and its Mn(II) Co(II) Ni(II) Cu(II) Zn(II) and VO(II) metal complexes were carried out. These compounds were characterized by Mass 1H-NMR FT-IR Elemental analysis Molar conductance Magnetic susceptibility UV-Vis. P-XRD TGA etc. and were screened for biological activities.
Synthesised azo-Schiff base ligand and its metal complexes were evaluated for their antimicrobial antidiabetic as well as anticáncer activities against various bacteria and fungi and MCF-7 breast cancer cell line respectively.
From the findings of various results we can conclude that the synthesized metal complexes exhibit higher biological activities than the azo-Schiff base ligand.
Antibacterial and Insecticidal Activities of Bacillus licheniformis SKS7 Methanolic Extract
Microbes are a rich source of antibacterial and anti-insect molecules. Due to rising antibiotic and anti-insect resistance in various sectors of the society it is important to identify new compounds that may address these issues.
This study aimed to explore the bacteria isolated from soil to identify new molecules with antibacterial and anti-insect activity. Further the current study is aimed at testing and characterizing antimicrobial and insecticidal properties of methanolic extracts from four different soil bacteria.
This study reports the isolation and characterization of soil bacteria by morphological biochemical and molecular analysis. The antibacterial potential of methanolic extracts of four bacterial strains were tested using an agar well diffusion assay along with studying their insecticidal effects on the development and survival of Spodoptera litura. Fractionation of the methanolic extract was performed by chromatography and the separated fractions were tested for their antibacterial activity.
The bacteria belong to Bacillus Exiguobacterium and Microbacterium species. The extract of Bacillus licheniformis SKS7 exhibited maximum antibacterial activity against all tested microbes including human pathogens. Extract from the same microbe also showed maximum anti-insect activity against Spodoptera litura by significantly increasing the pupal period by as much as 80% and hence extending the time to adult emergence. Morphological abnormalities like deformed wings deformed pupae and failure to emerge from pupae were also observed. Purification of the extract by HPLC and gel permeation chromatography helped us to observe a low molecular weight protein that may be responsible for its antibacterial activity.
Methanolic extract of Bacillus licheniformis SKS7 contains bioactive molecules with antibacterial and anti-insect activities. Further characterization and identification of these molecules may form the basis for the development of novel antibacterial drugs and insecticidal molecules in the future.
Antimicrobial, Antifungal, and Insecticidal Activities of Scolymus grandiflorus Essential Oil Rich in Davanoid Compounds
This study explores the antimicrobial antifungal and insecticidal properties of Scolymus grandiflorus essential oil examining its potential uses in the fields of pharmacology and agriculture.
The essential oil obtained by hydrodistillation was studied by GC and GC/MS. The antibacterial capacity of the essential oil was determined against two Gram-positive and three Gram-negative bacterial species. The antifungal activity of the essential oil was investigated against two fungi responsible for many fruit and vegetable diseases. The insecticidal activity of essential oil was evaluated against larvae pupae and adult flies of Ceratitis capitata.
The GC and GC-MS analysis of the essential oil of the roots of S. grandiflorus revealed the predominant presence of davanoids representing more than 80% of its chemical composition. The results of the disc diffusion test showed significant antimicrobial activity. The essential oil inhibited the growth of Salmonella typhi (25 mm) Staphylocoque aureus (18 mm) and Escherichia coli (17 mm) with inhibition diameters comparable to those of gentamicin. The essential oil significantly inhibited mycelial growth with up to 98% inhibition for Fusarium solani and 73% for Alternaria alternata at 8 µL/mL. Insecticidal activity was most pronounced on adult flies followed by pupae and finally larvae.
Tests on the essential oils of S. grandiflorus revealed promising characteristics as insecticidal antifungal and antimicrobial agents. These results could be used in the development of new solutions to control pathogens responsible for plant diseases and mycotoxin-producing organisms.
In vitro Tolerance of Staphylococcus haemolyticus and Candida albicans Biofilms to Dalbavancin and Anidulafungin
Concerns about infections resulting from bacterial biofilm formation in invasive devices such as catheters and prostheses are becoming widespread in the public health domain. Staphylococcus haemolyticus a coagulase-negative bacterium and Candida albicans a yeast have become recurrent pathogens of these diseases because their presence in these devices enhances the likelihood of infection. It is believed that these microorganisms produce biofilms which complicate treatment and slow the patient´s recuperation. Dalbavancin is a semisynthetic lipoglycopeptide-class antibiotic utilized as an anti-infective agent to break down gram-positive bacteria biofilms. Anidulafungin is an echinocandin class antifungal medication that works very well against resistant yeast strains and removes biofilms.
This study aims to examine the anti-infective agents´ tolerance to the biofilms of Staphylococcus haemolyticus and Candida albicans.
Polymicrobial biofilms were grown in a CDC Biofilm Reactor (CBR) for use in in vitro experiments.
When dalbavancin maintained its antibiotic activities against Staphylococcus haemolyticus in comparison with their activity against the sessile forms the antifungal anidulafungin lost efficacy in eliminating Candida albicans.
The planktonic forms of microbes are examined in relation to the tolerance to these anti-infective drugs.
Recent Advancement in Pyrazole Derivatives as Antimalarial Agents and their SAR Study
Malaria is caused by protozoan parasites and is a significant contributor to global mortality and morbidity. The main reasons for the resurgence of malaria are the emergence of drug-resistant strains of the parasite and the ineffectiveness of current treatment. Pyrazole-based drugs play a crucial role in medicinal chemistry due to their diverse pharmacological properties. The pyrazole structure a five-membered ring with two nitrogen atoms is a key pharmacophore in various therapeutic agents. Numerous derivatives of pyrazole scaffold exhibited a wide range of pharmacological activity such as analgesics antiinflammatory antioxidant antimicrobial antidiabetic anticancer antiviral antifungal and antithrombotic activities. These drugs provide numerous opportunities for enhancing antimalarial agents by targeting various critical receptors. Various pyrazole derivatives have been reported to inhibit enzymes receptors and other targets to manage malaria. These derivatives inhibited parasite through various mechanisms such as falcipain dihydrofolate redcutase dihydroorotate dehydrogenase lactate dehydrogenase protein kinase calcium dependent protein kinase glycogen synthase kinase and histo aspartic protease. Currently researchers are developing new pyrazole-based derivatives often in combination with other moieties for improved malaria treatment. This review highlights the recent therapeutic advancements of pyrazole including its structure-activity relationship molecular docking commercial drug availability and a summary of recent research publications all of which collectively assist scientists in developing effective drugs with desired pharmacological activities.
Beyond the Surface: Tracing the Evolution of Inflammatory Mechanism in Depression through Bibliometric Analysis
Depression is a common mental illness that has become a major economic burden worldwide. Recently increasing evidence has highlighted the inflammatory mechanism of depression. In order to understand the research status of this field this study used the bibliometric analysis method to overview the research content and progress as well as analyze the development trend and limitations.
In this study articles and reviews were included in the specific search strategy. The matched papers were exported from the Web of Science database. CiteSpace 6.3 R1 and Bibliometrix (R package) were utilized to generate bibliometric and knowledge maps.
A total of 25063 articles were included in this study. The number of publications in this field has gradually increased especially in recent years. These papers come from 156 countries led by the United States and China mainland. The leading research institution is the University of Toronto (Canada). Brain Behavior and Immunity is the journal with the most publications and the most frequently co-cited journals. Among 91100 authors Maes M has the most publications and co-citations. According to the keywords burst and co-cited reference analysis the hotspots in the field in recent years include kynurenine c-reactive protein neuroinflammation and gut microbiota.
Although abundant academic achievements have been made on the inflammatory mechanism of depression there is still a long way to go before these research results can be applied to clinical practice. Strengthening international academic exchanges and cooperation may promote breakthroughs in this field.
An Overview of Nipah Virus Infection
Nipah virus (NiV) a bat-borne infection was first identified in Malaysia 20 years ago and has since caused outbreaks in South and Southeast Asia. NiV leads to severe respiratory and neurological conditions is often fatal and is highly contagious spreading through close contact with infected individuals or animals. The virus exhibits varied clinical and epidemiological traits necessitating rapid infection control measures to prevent epidemics. Despite advances in molecular and serological diagnostic techniques effective treatment and prevention interventions remain unavailable. The high fatality rate and potential for widespread transmission underscore the urgent need for effective therapies. The “One Health” approach is vital for preventing NiV infection as bats are the primary transmission route to humans though other intermediary hosts exist. Initially NiV infections presented as fever and rapid brain function deterioration after contact with pigs. Recent outbreaks have shown pronounced respiratory symptoms and human-to-human transmission. The pandemic potential of NiV is significant due to the ubiquity of its reservoir host increased deforestation multiple transmission modes high case fatality rate and lack of effective treatments or vaccines. This review explores the microbiology epidemiology and current treatment and vaccination research for NiV.
Unveiling the Potency: Synthesis and Assessment of Antimicrobial Potential of Some Bis(indolyl)methane Derivatives
The urgent need for new antimicrobial compounds arises from the growing threat of multidrug-resistant human pathogens responsible for infectious diseases. The indole moiety a prevalent heterocyclic ring system found in nature is a key structural element in many pharmaceutical agents due to its wide range of biological activities. Bis(indolyl)methanes in particular have emerged as promising candidates for antibacterial activity.
This study aimed to evaluate the antibacterial activity of nine bis(indolyl)methane derivatives against a range of pathogenic bacterial strains responsible for various human diseases.
The compounds were synthesized using a solvent-free method and their antibacterial activity was evaluated using the disk diffusion assay. The minimum inhibitory concentration (MIC) of the active compounds identified in the disk diffusion assay was determined by the microtiter broth dilution method in 96-well microtiter plates. Bacterial strains in the mid-log phase of growth were utilized. Bacterial suspensions equivalent to 0.5 McFarland standards were prepared by suspending the bacterial inoculum in sterile water. A working concentration of 100 µg/mL was achieved by diluting the test compounds in 100% DMSO.
The antimicrobial activity of nine synthetic compounds was evaluated against nine medically significant pathogenic strains. These include Pseudomonas aeruginosa Bacillus cereus and Shigella flexneri known for producing toxins that cause acute foodborne illnesses as well as Escherichia coli K12 and Enterococcus faecalis which can disrupt the intestinal barrier in immunocompromised individuals. The results suggest that these compounds have the potential to be effective antimicrobial agents.
Our findings demonstrate the promising antimicrobial activity of the synthesized compounds with 1-ethyl-3-((1-ethyl-1H-indol-3-yl)(phenyl)methyl)-1H-indole emerging as the most potent significantly inhibiting most tested bacterial strains. These results highlight the potential for developing novel compounds for antibacterial treatment.
Cardiovascular Findings and Effects of Caffeine on Experimental Hypothyroidism
Thyroid hormone deficiencies can disrupt organ functions significantly impacting the cardiovascular system. Recently the effects of thyroid hormones on the heart have garnered increased attention. However most studies are conducted on humans using clinical data while cellular-level and experimental studies remain limited.
This study aimed to investigate the cardiovascular implications of hypothyroidism and evaluate the impact of caffeine on cardiac health in rats induced with hypothyroidism using propylthiouracil (PTU).
The study involved 60 rats divided into six groups. Group 1 served as the untreated control. Group 2 received PTU for two months to induce hypothyroidism. Group 3 received PTU for one month followed by caffeine for one month. Group 4 received caffeine for two months. Group 5 received both PTU and caffeine simultaneously for two months. Group 6 received PTU for one month followed by one month under normal conditions.
During necropsy normal thyroid glands were observed in Groups 1 4 and 6 enlarged thyroids in Group 2 and smaller thyroids in Groups 3 and 5. Microscopic examination revealed varying thyroid histologies: Group 2 showed significant epithelial cell proliferation and absent colloid while Groups 3 5 and 6 had altered yet colloid-containing acini. Macroscopic inspection of hearts appeared normal across all groups. However histopathological examination revealed significant hyperemia and microhemorrhages in Group 2 contrasting with normal findings in other groups. Immunohistochemical analysis indicated reduced cardiac troponin expression in Group 2 while other groups maintained prominent expression. Additionally Group 2 displayed increased serum TSH levels and decreased T3 and T4 levels.
The findings suggest that administering caffeine alongside or after PTU treatment in rats with experimentally induced hypothyroidism may ameliorate thyroid and cardiac irregularities. This study indicates caffeine's potential in mitigating the adverse effects of hypothyroidism on thyroid and heart health.
Gut Microbiota and Diabetes: Pioneering New Treatment Frontiers
Diabetes Mellitus (DM) is a complex metabolic disorder characterized by chronic hyperglycemia and poses significant global health challenges. Conventional treatments such as insulin therapy and lifestyle modifications have shown limited efficacy in addressing the multifactorial nature of DM. Emerging evidence suggests that gut microbiota a diverse community of microorganisms critical for metabolism and immune function plays a pivotal role in metabolic health. Dysbiosis an imbalance in gut microbiota composition has been linked to insulin resistance obesity and DM. Gut microbiota influences glucose metabolism through mechanisms including short-chain fatty acid production gut permeability regulation and immune system interactions indicating a bidirectional relationship between microbial health and metabolism. Clinical and experimental studies demonstrate that modulating gut microbiota through dietary interventions (prebiotics probiotics synbiotics) improves glycemic control and insulin sensitivity in DM patients. Fecal Microbiota Transplantation (FMT) has also shown promise in restoring healthy gut microbiota and alleviating DM-related metabolic disturbances. However challenges remain including the need for personalized treatments due to individual microbiota variability and the unknown long-term effects of these interventions. Future research should focus on elucidating the mechanisms by which gut microbiota influences metabolism and refining personalized approaches to enhance DM management.
Interlinking the Cross Talk on Branched Chain Amino Acids, Water Soluble Vitamins and Adipokines in the Type 2 Diabetes Mellitus Etiology
Type 2 Diabetes Mellitus (T2DM) is an etiologically diverse metabolic dysfunction that if untreated leads to chronic hyperglycemia. Understanding the etiology of T2DM is critical as it represents one of the most formidable medical challenges of the twenty-first century. Traditionally insulin resistance has been recognized as the primary risk factor and a well-known consequence of type 2 diabetes. Emerging evidence suggests that branched-chain amino acids (BCAAs) adipokines and deficiencies in water-soluble vitamins such as thiamine and pyridoxine play significant roles in the development of insulin resistance a key feature of T2DM. These factors are interconnected through the AMP-activated protein kinase (AMPK) pathway which regulates various metabolic processes including glucose transport lipid synthesis and inflammatory responses. Dysregulation of AMPK is linked to insulin resistance and metabolic syndrome-related illnesses. Understanding the interplay between BCAAs adipokines vitamins and AMPK may offer new therapeutic targets for the prevention and treatment of diabetes mellitus.
Recent Outbreaks and Factsheet of Future Global Pandemic Marburg Virus: A Looming Threat
The Marburg virus (MARV) which belongs to the family Filoviridae is the cause of Marburg virus disease (MVD) a disease that can be fatal. Laboratories employees of Marburg and Frankfurt cities of Germany and Belgrade city of Yugoslavia (now Serbia) contracted an infection caused by a hitherto unidentified infectious pathogen in August 1967. According to the World Health Organization (WHO) MARV is one of the most important issues in the world. With a case fatality rate ranging from 24.0 to 88.0% the virus is very dangerous underscoring the need for public awareness. This outbreak was determined to be caused by the MARV one of the deadliest viruses that infect humans. However African green monkeys (Chlorocebus aethiops) which were imported from Uganda and transported to all three locations were discovered to be the virus's primary source while fruit bats (Rosettus aegyptiacus) which belong to the Pteropodidae family act as the MARV's natural hosts. The disease's pathophysiology indicates significant antiviral suppression as a result of alterations in gene expression and the synthesis of interferon-stimulated genes in the hepatic cells. Along with the advent of hemorrhagic manifestations which can result in a patient's death the condition may worsen and cause abdominal discomfort nausea vomiting pharyngitis diarrhea and other symptoms. The countermeasures against MVD are outlined in this article with an emphasis on the ecology traits virion proteins pathology and transmission of MARV clinical aspects along with diagnostic patient therapy and management.
Revolutionizing Quinolone Development for DNA Gyrase Targeting; Discovering the Promising Approach to Fighting Microbial Infections
DNA gyrase is a type II topoisomerase enzyme that can cause negative supercoiling in DNA by using the energy produced by ATP hydrolysis. There are two main types of topoisomerases: type I and type II. Type I enzymes cut a single strand of DNA and are further classified as type IA if they connect to a 5′ phosphate of DNA or type IB if they link to a 3′ phosphate. Type II topoisomerases break both strands creating a staggered double-strand break. Antimicrobial resistance is a major concern for the global healthcare system. Resistance is the ability of microorganisms to neutralize and withstand antimicrobial drugs previously used to treat microbial infections. Some known classes of DNA gyrase inhibitors are coumarins cyclothialidines and quinolones. Antimicrobial medicines such as quinolones have been widely used to treat microbiological diseases. However the increased use of quinolones has led to the emergence of quinolone-resistant bacteria which poses a serious risk to public health. Microorganisms can cause resistance due to changes in the target enzymes DNA gyrase and topoisomerase IV which are responsible for transcription and DNA replication. Additionally differences in drug entry and efflux may also play a role in resistance. Plasmids that produce the Qnr protein can mediate resistance to quinolones by protecting the quinolone targets from inhibition. This review aims to revolutionize the discovery of quinolone-based antibiotics specifically targeting DNA gyrase a critical enzyme in bacterial DNA replication to enhance the efficacy and specificity of anti-microbail agents against microbial infections.
Long-term Remission in Functioning Pituitary Adenomas after Medical Therapy Withdrawal: A Chance for Cushing’s Disease
The possibility of sustained disease remission in functioning pituitary adenomas after drug withdrawal is well-known for prolactinomas and it has also been described in a subset of acromegalic patients. On the contrary medical treatment for Cushing’s Disease (CD) is generally considered a life-long measure except for previously radio-treated patients. Sparse evidence of spontaneous remissions in CD has been reported mainly related to a possible pituitary tumor apoplexy. To the best of our knowledge none of these cases has included the use of a pituitary targeting agent.
Herein we have reported the case of a radiotherapy-naïve patient with persistent CD after pituitary surgery who participated in the CSOMG230 trials presenting sustained remission after Long-acting Release (LAR) pasireotide withdrawal. Under monthly pasireotide LAR 40 mg the patient achieved urinary hormone control and clinical signs of cortisol excess normalization. After 8 years of treatment the patient completed the study protocol and had to withdraw the drug as it was no longer available for CD in Italy. Before starting new therapies we reassessed hormone levels that were surprisingly within normal ranges. At 24 months after the last dose of pasireotide the patient was still in clinical and biochemical full remission. We have also briefly reviewed previous cases of sustained remission after somatostatin analogues withdrawal in other functioning pituitary adenomas.
Far from the general rule this case suggests that prolonged treatment with pasireotide LAR might induce a durable CD remission. A dose down-titration/suspension might be considered in patients well-controlled on long-term therapy and with negative pituitary imaging. However close monitoring is recommended given the high rate of complications in untreated patients.
Evaluating the Relationship between Cathepsins and Papillary Thyroid Carcinoma: A Mendelian Randomization Study
Papillary Thyroid Carcinoma (PTC) is the most common thyroid cancer with an etiology and progression that are not fully understood. Research suggests a link between cathepsins and PTC but the causal nature of this link is unclear. This study uses Mendelian Randomization (MR) to investigate if cathepsins causally influence PTC risk.
We applied univariable and multivariable MR analyses using genetic variants as proxies for cathepsin levels. Genetic data for cathepsins were sourced from the INTERVAL study while PTC data came from the Finnish Genome-Wide Association Study database. Our analysis employed several MR methods including the Inverse Variance Weighted (IVW) approach MR-Egger and the Weighted Median method to provide comprehensive insights and address possible pleiotropy.
MR findings suggest a significant causal association between higher cathepsin levels and increased PTC risk. Notably genetic variants indicating higher cathepsin Z expression were positively causal associated with PTC risk (OR:1.1190 95% CI: 1.0029-1.2486) multivariable analysis confirmed significant carcinogenesis role of cathepsin Z in PTC (OR: 1.1593 95% CI: 1.0137-1.3258) with results consistent across various tests indicating a robust relationship.
This study established a causal link between cathepsin levels and PTC risk emphasizing the roles of cathepsin Z in its progression. These insights could lead to new therapeutic strategies targeting these enzymes. Further research is necessary to understand the underlying biological mechanisms and their clinical implications.
Pharmacological Activities of Warm Alkaline Hydrogen Peroxide Solution and Therapeutic Potential in Medicine: Physical-Chemical Reprofiling as a Promising Lead for Drug Discovery
The traditional use of antiseptics chemotherapeutic expectorant mucolytic drugs and oxygen gas by artificial ventilation does not effectively eliminate hypoxemia in sputum mucus pus and blood asphyxia in COVID-19. The emergency conversion of sputum mucus pus and blood into oxygenated foam inside the airways utilizing the enzyme catalase and warm alkaline hydrogen solutions (WAHPSs) is proposed as a promising area for new therapeutic development. The possibility of physical-chemical repurposing of hydrogen peroxide from an antiseptic in pyolytics mucolytics hemolytics and oxygen-producing antihypoxants by converting a cold acidic non-carbonated drug into an oxygen-saturated WAHPS and its intrapulmonary injection is pointed out as a way to solve this problem. The possibility of medically enriching blood oxygen in hypoxemia by catalase cleavage of hydrogen peroxide when WAHPSs are administered orally as energy drinks or directly into the blood as injections is pointed out. The fact is that virtually all human tissues are rich in catalase which immediately breaks down hydrogen peroxide into water and oxygen gas. Inhalation and/or intrapulmonary injections of WAHPSs have been shown to provide intra-airway interaction with catalase in sputum mucus pus and/or blood and releases oxygen gas which foams the biological masses is absorbed into the blood and eliminates hypoxemia. Thus the physical-chemical repurposing of known drugs can be considered a promising direction for the discovery of new drugs.
Value of the data:
1) Why are these data useful?
These studies indicate that the enzyme catalase which is present in many tissues of animals and humans in both normal and disease can be employed to enrich the tissues with oxygen and eradicate hypoxia when hydrogen peroxide solution is injected into them.
2) Who can benefit from these data?
Mountaineers divers submarine sailors miners astronauts traumatologists resuscitators cardiologists transplantologists pulmonologists obstetricians and gynecologists emergency physicians EMERCOM personnel and medical workers providing emergency medical care in cases of smoke in rooms lack of oxygen in the inhaled air drowning bronchial asthma attack acute respiratory distress syndrome and asphyxia can use the data presented in this article.
3) How can these data be used/reused for further insights or development of experiments?
These data can be used to develop new antihypoxants to improve methods of increasing the organism's endurance to hypoxia methods of organ and tissue preservation methods of ischemia treatment methods of emergency medical care in urgent conditions methods of ARDS treatment and standards of medical care.