Synthesis, Characterization, and Evaluation of Silver Nanoparticle-Loaded Carboxymethyl Chitosan with Sulfobetaine Methacrylate Hydrogel Nanocomposites for Biomedical Applications.

In this study, nanocomposites of AgNPs encapsulated in carboxymethyl chitosan (CMCS) with sulfobetaine methacrylate (SB) hydrogel (AgNPs/CMCS-SB) were synthesized. The UV-Vis spectra indicated the presence of AgNPs, with a broad peak at around 424 nm, while the AgNPs-loaded CMCS-SB nanocomposite exhibited absorption peaks at 445 nm. The size and dispersion of AgNPs varied with the concentration of the AgNO3 solution, affecting swelling rates: 148.37 ± 15.63%, 172.26 ± 18.14%, and 159.17 ± 16.59% for 1.0 mM, 3.0 mM, and 5.0 mM AgNPs/CMCS-SB, respectively. Additionally, water absorption capacity increased with AgNPs content, peaking at 11.04 ± 0.54% for the 3.0 mM AgNPs/CMCS-SB nanocomposite. Silver release from the nanocomposite was influenced by AgNO3 concentration, showing rapid initial release followed by a slower rate over time for the 3.0 mM AgNPs/CMCS-SB. XRD patterns affirmed the presence of AgNPs, showcasing characteristic peaks indicative of a face-centered cubic (fcc) structure. The FTIR spectra highlighted interactions between AgNPs and CMCS-SB, with noticeable shifts in characteristic bands. In addition, SEM and TEM images validated spherical AgNPs within the CMCS-SB hydrogel network, averaging approximately 70 and 30 nm in diameter, respectively. The nanocomposite exhibited significant antibacterial activity against S. aureus and E. coli, with inhibition rates of 98.9 ± 0.21% and 99.2 ± 0.14%, respectively, for the 3.0 mM AgNPs/CMCS-SB nanocomposite. Moreover, cytotoxicity assays showcased the efficacy of AgNPs/CMCS-SB against human colorectal cancer cells (HCT-116 cells), with the strongest cytotoxicity (61.7 ± 4.3%) at 100 µg/mL. These results suggest the synthesized AgNPs/CMCS-SB nanocomposites possess promising attributes for various biomedical applications, including antimicrobial and anticancer activities, positioning them as compelling candidates for further advancement in biomedicine.

From port to planet: Assessing NO2 pollution and climate change effects with Sentinel-5p satellite imagery in maritime zones.

The growing effects of climate change on Malaysia's coastal ecology heighten worries about air pollution, specifically caused by urbanization and industrial activity in the maritime sector. Trucks and vessels are particularly noteworthy for their substantial contribution to gas emissions, including nitrogen dioxide (NO2), which is the primary gas released in port areas. The application of advanced analysis techniques was spurred by the air pollution resulting from the combustion of fossil fuels such as fuel oil, natural gas and gasoline in vessels. The study utilized satellite photos captured by the Tropospheric Monitoring Instrument (TROPOMI) on the Sentinel-5P satellite to evaluate the levels of NO2 gas pollution in Malaysia's port areas and exclusive economic zone. Before the COVID-19 pandemic, unrestricted gas emissions led to persistently high levels of NO2 in the analyzed areas. The temporary cessation of marine industry operations caused by the pandemic, along with the halting of vessels to prevent the spread of COVID-19, resulted in a noticeable decrease in NO2 gas pollution. In light of these favourable advancements, it is imperative to emphasize the need for continuous investigation and collaborative endeavours to further alleviate air contamination in Malaysian port regions, while simultaneously acknowledging the wider consequences of climate change on the coastal ecology. The study underscores the interdependence of air pollution, maritime activities and climate change. It emphasizes the need for comprehensive strategies that tackle both immediate environmental issues and the long-term sustainability and resilience of coastal ecosystems in the context of global climate challenges.

Anti-Diabetic, Anti-Cholinesterase, and Anti-Inflammatory Potential of Plant Derived Extracts and Column Semi-Purified Fractions of Ficus benghalensis.

BACKGROUND: The present study aimed to investigate the in-vitro anti-diabetic, anti-cholinesterase, and anti-inflammatory potential of extracts from different parts of Ficus benghalensis, including leaves, stem, and roots, as well as isolated column fractions (F-B-1 C, F-B-2 C, F-B-3 C, and F-B-4 C). METHODS: The extracts and subsequent fractions were evaluated for their inhibitory activity against key enzymes involved in diabetes [α-glucosidase and α-amylase], neurodegenerative diseases [acetylcholinesterase and butyrylcholinesterase], and inflammation (cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX)). RESULTS: The results showed that F. benghalensis leaf extract exhibited the highest α-glucosidase inhibitory activity (73.84%) and α-amylase inhibitory activity (76.29%) at 1000 µg/mL. The stem extract (65.50%) and F-B-2 C fraction (69.67%) also demonstrated significant α-glucosidase inhibitory activity. In terms of anti-cholinesterase activity, the extracts of roots, leaves, and stem showed promising inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), with half maximal inhibitory concentration (IC50) values ranging from 50.50 to 474.83 µg/mL. The derived fractions (F-B-1 C, F-B-2 C, F-B-3 C, and F-B-4 C) also exhibited notable inhibition of AChE and BChE, with IC50 values from 91.85 to 337.94 µg/mL. Moreover, the F-B-3 C fraction demonstrated the highest COX-2 inhibitory potential (85.72%), followed by F-B-1 C (83.13%), the stem extract (80.85%), and the leaves extract (79.00%). The F-B-1 C fraction showed the highest 5-LOX inhibitory activity (87.63%), while the root extract exhibited the lowest inhibition (73.39%). CONCLUSIONS: The results demonstrated promising bioactivity, suggesting the potential of F. benghalensis as a source of natural compounds with therapeutic applications. Further studies are required to identify and isolate the active components responsible for these effects and to evaluate their in-vivo efficacy and safety.

Hypoglycemic, anti-inflammatory, and neuroprotective potentials of crude methanolic extract from Acacia nilotica L. - results of an in vitro study.

Acacia nilotica L., also known as babul, belonging to the Fabaceae family and the Acacia genus, is typically used for ornamental purposes and also as a medicinal plant found in tropical and subtropical areas. This plant is a rich source of bioactive compounds. The current study aimed to elucidate the hypoglycemic, anti-inflammatory, and neuroprotective potential of A. nilotica's crude methanolic extract. The results of the in vitro antidiabetic assay revealed that methanolic extract of A. nilotica inhibited the enzyme α-glucosidase (IC50: 33 µg mL-1) and α-amylase (IC50: 17 µg mL-1) in a dose-dependent manner. While in the anticholinesterase enzyme inhibitory assay, maximum inhibition was shown by the extract against acetylcholinesterase (AChE) (637.01 µg mL-1) and butyrylcholinesterase (BChE) (491.98 µg mL-1), with the highest percent inhibition of 67.54% and 71.50% at 1000 µg mL-1, respectively. This inhibitory potential was lower as compared to the standard drug Galantamine that exhibited 82.43 and 89.50% inhibition at the same concentration, respectively. Moreover, the methanolic extract of A. nilotica also significantly inhibited the activities of cyclooxygenase 2 (COX-2) and 5-lipoxygenase (5-LOX) in a concentration-dependent manner. The percent inhibitory activity of 5-LOX and COX-2 ranged from 42.47% to 71.53% and 43.48% to 75.22%, respectively. Furthermore, in silico, in vivo, and clinical investigations must be planned to validate the above-stated bioactivities of A. nilotica.

Evaluating climate change impacts on reef environments via multibeam echosounder and Acoustic Doppler Current profiler technology.

Crucial to the Earth's oceans, ocean currents dynamically react to various factors, including rotation, wind patterns, temperature fluctuations, alterations in salinity and the gravitational pull of the moon. Climate change impacts coastal ecosystems, emphasizing the need for understanding these currents. This study explores multibeam echosounder (MBES), specifically R2-Sonic 2020 instrument, offering detailed seabed information. Investigating coral reefs, rocky reefs and artificial reefs aimed to map seafloor currents movement and their climate change responses. MBES data viz. Bathymetry and backscatter were classified and acoustic doppler current profiler (ADCP) ground data were validated using random forest regression. Results indicated high precision in currents speed measurement i.e. coral reefs with 0.96, artificial reefs with 0.94 and rocky reefs with 0.97. Currents direction accuracy was notable in coral reefs with 0.85, slightly lower in rocky reefs with 0.72 and artificial reefs with 0.60. Random forest identified sediment and backscatter as key for speed prediction while direction relies on bathymetry, slope and aspect. The study emphasizes integrating sediment size, backscatter, bathymetry and ADCP data for seafloor current analysis. This multibeam data on sediments and currents support better marine spatial planning and determine biodiversity patterns planning in the reef area.

Aggregation operators on group-based generalized q-rung orthopair fuzzy N-soft sets and applications in solar panel evaluation.

Every problem in decision-making has a solution when the information that is available is properly and precisely modeled. This study focuses on non-binary data from N-soft sets and q-rung orthopair fuzzy values, referred to as group-based generalized q-rung orthopair fuzzy N-soft sets (GGq-ROFNSSs). The GGq-ROFNSSs model provides information simultaneously on numerous competing criteria, alternatives, sub-alternatives, and data summarization. We introduce properties of GGq-ROFNSSs such as distinct inclusion features of GGq-ROFNSSs, weak complements of the GGq-ROFNSS, top weak complements the GGq-ROFNSS, bottom weak complements the GGq-ROFNSS. We provide the notion of GGq-ROFNSWA and GGq-ROFNSWG operators as well as their idempotency, monotonicity, and boundedness features. The notion of GGq-ROFNSSs requires a sound methodology of multiple criteria decision making (MCDM) since GGq-ROFNSS combines numerous elements of complex decision-making. We provide a MCDM methodology for the GGq-ROFNSWA and GGq-ROFNSWG operators and depict it in a flowchart. The selection of solar panels for a city is a difficult procedure because it depends on several components such as environment, where the area is located, what kinds of needs are being met, etc. We find a solution to the problem of selecting a suitable solar panel for a city with their underlying characteristics. Finally, we provide a comparison of the suggested method with other techniques to demonstrate its advantages.

Evaluation of Habenaria aitchisonii Reichb. for antioxidant, anti-inflammatory, and antinociceptive effects with in vivo and in silico approaches.

Habenaria aitchisonii Reichb was analyzed in this research, including its chemical composition and its in vitro antioxidant, anti-inflammatory, acute oral toxicity, and antinociceptive activity. The chloroform and ethyl acetate fractions were found to be the most powerful based on in vitro antioxidant, anti-inflammatory, and analgesic assays. The acute oral toxicity of the crude methanolic extract was determined before in vivo studies. The acetic acid and formalin tests were used to measure the antinociceptive effect, and the potential mechanisms involved in antinociception were explored. The carrageenan-induced paw edema test was used to examine the immediate anti-inflammatory effect, and many phlogistic agents were used to determine the specific mechanism. Furthermore, for ex vivo activities, the mice were sacrificed, the forebrain was isolated, and the antioxidant levels of glutathione (GSH), superoxide dismutase (SOD), thiobarbituric acid reactive substances (TBARS) and catalase (CAT) were estimated using a UV spectrophotometer. No toxicity was seen at oral dosages up to 3,000 mg/kg. The antinociceptive impact was much higher than the standard drug. Both the inflammatory and neurogenic phases of the formalin experiment revealed an analgesic effect in the chloroform and ethyl acetate fractions. In carrageenan anti-inflammatory assays, the chloroform fraction (Ha.Chf) was the most potent fraction. We further studied the GC-MS of crude plant extract and found a total of 18 compounds. In the anti-inflammatory mechanism, it was observed that the Ha.Chf inhibits the COX-2 as well as 5-LOX pathways. The results exhibited that this species is a good source of phytocomponents like germacrone, which can be employed as a sustainable and natural therapeutic agent, supporting its traditional use in folk medicine for inflammatory conditions and pain.

Does green investment affect environment pollution: Evidence from asymmetric ARDL approach?

Pollution in the environment is today the biggest issue facing the globe and the main factor in the development of many fatal diseases. The main objective of the study to investigate green investments, economic growth and financial development on environmental pollution in the G-7 countries. This study used annual penal data from 1997 to 2021. The panel NARDL (Non-linear autoregressive distributed lag) results affirm that the positive change of green investment and negative shock in green investment have a significant and positive association with environment pollution in G-7 nations. Our findings provide more evidence for the long-term asymmetry between financial development and environmental performance. However, the findings confirm that a positive modification in financial development has a positive and significant effect on environment pollution. Whereas negative shock in financial development is negative and insignificant relationship with environment pollution. Moreover, the outcomes of the study reveal that both positive shock in gross domestic product growth and negative shock of economic growth have a significant and positive link with environment pollution in G-7 countries. According to the findings, by lowering carbon dioxide emissions, green investments reduced environmental pollution in the G-7 nations over the long and short term. Moreover, it is an innovative research effort that provides light on the connection between green investments, financial development, and the environment while making mention to the EKC in G-7 countries. After all these, our recommendation is to increases green investment expenditures to reduce environmental pollution in the G-7 nations based on our findings. Additionally, one important way for the nation to achieve its sustainable development goals is to improve advancements in the financial sector.

Exploitation of the multitarget role of new ferulic and gallic acid derivatives in oxidative stress-related Alzheimer's disease therapies: design, synthesis and bioevaluation.

Monoamine oxidases (MAOs) inhibitors could decrease reactive oxygen species (ROS) generation, enhance mono-aminergic neural transmission, and have major therapeutic benefits for the treatment of Alzheimer's disease (AD). Following the conjunction of ferulic acid (FA)/gallic acid (GA) with sulfonamide, alanine and 2-aminobenzothiazole, we planned to assess the radical scavenging and antioxidant properties of synthesized analogs by using 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and ferric ion reducing antioxidant power (FRAP) assays. GA analog 28 was identified as the most potent antioxidant compound with IC50 values of 1.77 µM and 2.06 µM in DPPH and ABTS assays respectively. In the in vitro enzyme inhibition assays, synthesized derivative 23 emerged as a potent multitarget inhibitor of hMAO-B, eeAChE. COX-2 and 5-LOX with IC50 values of 0.037 µM, 0.071 µM, 14.3 µM and 0.59 µM, respectively. Moreover, selected compounds 23, 25, 26 and 28 displayed good to moderate inhibition of self-mediated amyloid ß1-42 peptide aggregation. More importantly, compounds 23, 25, 28 and 29 showed no neurotoxicity on SH-SY5Y cells and also showed excellent neuroprotective effects against H2O2-induced SH-SY5Y cells. In the in vivo experiment, antioxidant enzymes superoxide dismutase (SOD), catalase and glutathione peroxidase (GSH-Px) were studied in the brain of male BALB/c mice at the dose of 5 mg kg-1. All the tested compounds, except 29, have shown good to in vivo antioxidant potential. Docking studies on 3D crystallographic structures of AChE and MAO-B showed significant interactions with catalytic amino acid residues. In conclusion, the current study showed that FA/GA derivatives could be further exploited for their multitarget role in oxidative stress-related AD therapies.

Modification of 4-(4-chlorothiophen-2-yl)thiazol-2-amine derivatives for the treatment of analgesia and inflammation: synthesis and in vitro, in vivo, and in silico studies.

Inflammation is a protective response to a variety of infectious agents. To develop a new anti-inflammatory drug, we explored a pharmacologically important thiazole scaffold in this study. In a multi-step synthetic approach, we synthesized seven new thiazole derivatives (5a-5g). Initially, we examined the in vitro anti-inflammatory potentials of our compounds using COX-1, COX-2, and 5-LOX enzyme assays. After in vitro confirmation, the potential compounds were subjected to in vivo analgesic and anti-inflammatory studies. The hot plate method was used for analgesia, and carrageenan-induced inflammation was also assayed. Overall, all our compounds proved to be potent inhibitors of COX-2 compared to celecoxib (IC50 0.05 µM), exhibiting IC50 values in the range of 0.76-9.01 µM .Compounds 5b, 5d, and 5e were dominant and selective COX-2 inhibitors with the lowest IC50 values and selectivity index (SI) values of 42, 112, and 124, respectively. Similarly, in the COX-1 assay, our compounds were relatively less potent but still encouraging. Standard aspirin exhibited an IC50 value of 15.32 µM. In the 5-LOX results, once again, compounds 5d and 5e were dominant with IC50 values of 23.08 and 38.46 µM, respectively. Standard zileuton exhibited an IC50 value of 11.00 µM. Based on the COX/LOX and SI potencies, the compounds 5d and 5e were subjected to in vivo analgesic and anti-inflammatory studies. Compounds 5d and 5e at concentrations of 5, 10, and 20 mg/kg body weight were significant in animal models. Furthermore, we explored the potential role of compounds 5d and 5e in various phlogistic agents. Similarly, both compounds 5d and 5e were also significantly potent in the anti-nociceptive assay. The molecular docking interactions of these two compounds with the target proteins of COX and LOX further strengthened their potential for use in COX/LOX pathway inhibitions.

Investigation of anti-nociceptive, anti-inflammatory potential and ADMET studies of pure compounds isolated from Isodon rugosus Wall. ex Benth.

The strong ethnopharmacological utilization of Isodon rugosus Wall. Ex. Benth is evident in the treatment of several types of pain and inflammation, including toothache, earache, abdominal pain, gastric pain, and generalized body pain and inflammation. Based on this background, the antinociceptive effects of the crude extract, various fractions, and essential oil have been reported previously. In this research work, we isolate and characterize pure bioactive compounds from I. rugosus and evaluate possible mechanisms using various in vivo and in vitro models. The pure compounds were analyzed for analgesic and anti-inflammatory activities through various assays. The column chromatography of the chloroform fraction of I. rugosus led to the identification of two pure compounds, i.e., 1 and 2. Compound 1 demonstrated notable inhibition (62% writhing inhibition, 72.77% COX-2 inhibition, and 76.97% 5-LOX inhibition) and anti-inflammatory potential (>50% paw edema inhibition at various intervals). The possible mechanism involved in antinociception was considered primarily, a concept that has already been elucidated through the application of naloxone (an antagonist of opioid receptors). The involvement of adrenergic receptors was investigated using a hot plate model (an adrenergic receptor antagonist). The strong ethnomedicinal analgesic background of I. rugosus, supported by previous reports and current observations, leads to the conclusion that I. rugosus is a potential source of antinociceptive and anti-inflammatory bioactive compounds. It may be concluded from the results that the isolated analgesic compounds of I. rugosus may be a possible alternative remedy for pain and inflammation management with admirable efficacy and safety profiles.

Isolation, invitro, invivo anti-inflammatory, analgesic and antioxidant potential of Habenaria plantegania Lindl.

Habenaira plantaginea belong to orchid family which is native to Asia. Members of this family are commonly famous for the cure of pain and inflammation. To date, no research was found on isolation of compounds from this plant for the treatment of inflammation and analgesia nor has been published to our knowledge. The purpose of this study was to evaluate an analgesic, anti-inflammatory and anti-oxidant activity of the isolated compound from the most potent chloroform sub-fraction and the isolated compounds form the habenaria plantaginea. Anti-inflammatory analgesic and antioxidant potential of the various chloroform sub-fractions and isolated compounds from the most potent sub-fraction (HP-1 & HP-1) were screened for their in vitro enzymatic assays. Furthermore, prior to in-vivo investigation, the isolated compounds were subjected for their toxicity study. The potent compound was then examined for acetic acid-induced writhing, hot plate test, carrageenan-induced inflammation assays. Further various phlogistic agents were used for the evaluation of mechanism. In the COX-2 inhibitory assay the chloroform sub fraction Cf-4 demonstrated excellent activity as compared to the other sub-fraction with 92.15% inhibition. The COX-2 enzyme make prostaglandins which are directly involved in inflammation. Likewise against 5-LOX the Cf-4 was the most potent sub-fraction with IC50 3.77 µg/mL. The 5-LOX catalyzes the biosynthesis of leukotrienes which is a group of lipid mediators of inflammation derived from arachidonic acid. Free radicals can induce inflammation through cellular damage while chronic inflammation generates a large number of free radicals, whose eventually lead to inflammation. In antioxidant assays the Cf-4 fraction was displayed excellent results against ABTS, DPPH and H2O2 free radical with 88.88, 77.44, and 65.52% inhibition at highest concentration. Likewise, the compound HP-1 demonstrated 88.81, 89.34 and 80.43% inhibition while compound HP-2 displayed 84.34, 91.52 and 82.34% inhibition against ABTS, DPPH and H2O2 free radical which were comparable to the standard drug ascorbic acid respectively. This study's findings validate the use of this species as traditional use.

Exploring the Interactions between Obesity and Diabetes: Implications for Understanding Metabolic Dysregulation in a Saudi Arabian Adult Population.

The rising prevalence of obesity in Saudi Arabia is a major contributor to the nation's high levels of cardiometabolic diseases such as type 2 diabetes. To assess the impact of obesity on the diabetic metabolic phenotype presented in young Saudi Arabian adults, participants (n = 289, aged 18-40 years) were recruited and stratified into four groups: healthy weight (BMI 18.5-24.99 kg/m2) with (n = 57) and without diabetes (n = 58) or overweight/obese (BMI > 24.99 kg/m2) with (n = 102) and without diabetes (n = 72). Distinct plasma metabolic phenotypes associated with high BMI and diabetes were identified using nuclear magnetic resonance spectroscopy and ultraperformance liquid chromatography mass spectrometry. Increased plasma glucose and dysregulated lipoproteins were characteristics of obesity in individuals with and without diabetes, but the obesity-associated lipoprotein phenotype was partially masked in individuals with diabetes. Although there was little difference between diabetics and nondiabetics in the global plasma LDL cholesterol and phospholipid concentration, the distribution of lipoprotein particles was altered in diabetics with a shift toward denser and more atherogenic LDL5 and LDL6 particles, which was amplified in the presence of obesity. Further investigation is warranted in larger Middle Eastern populations to explore the dysregulation of metabolism driven by interactions between obesity and diabetes in young adults.

Revisiting the environmental Kuznets curve: assessing the impact of climate policy uncertainty in the Belt and Road Initiative.

Climate change repercussions such as temperature shifts and more severe weather occurrences are felt globally. It contributes to larger-scale challenges, such as climate change and biodiversity loss in food production. As a result, the purpose of this research is to develop strategies to grow the economy without harming the environment. Therefore, we revisit the environmental Kuznets curve (EKC) hypothesis, considering the impact of climate policy uncertainty along with other control variables. We investigated yearly panel data from 47 Belt and Road Initiative (BRI) nations from 1998 to 2021. Pooled regression, fixed effect, and the generalized method of moment (GMM) findings all confirmed the presence of inverted U-shaped EKC in BRI counties. Findings from this paper provide policymakers with actionable ideas, outlining a framework for bringing trade and climate agendas into harmony in BRI countries. The best way to promote economic growth and reduce carbon dioxide emissions is to push for trade and climate policies to be coordinated. Moreover, improving institutional quality is essential for strong environmental governance, as it facilitates the adoption of environmentally friendly industrialization techniques and the efficient administration of climate policy uncertainties.

Drug repurposing of FDA-approved anti-viral drugs via computational screening against novel 6M03 SARS-COVID-19.

OBJECTIVE: The COVID-19 pandemic has been recognized as severe acute respiratory syndrome, one of the worst and disastrous infectious diseases in human history. Until now, there is no cure to this contagious infection although some multinational pharmaceutical companies have synthesized the vaccines and injecting them into humans, but a drug treatment regimen is yet to come. AIM: Among the multiple areas of SARS-CoV-2 that can be targeted, protease protein has significant values due to its essential role in viral replication and life. The repurposing of FDA-approved drugs for the treatment of COVID-19 has been a critical strategy during the pandemic due to the urgency of effective therapies. The novelty in this work refers to the innovative use of existing drugs with greater safety, speed, cost-effectiveness, broad availability, and diversity in the mechanism of action that have been approved and developed for other medical conditions. METHODS: In this research work, we have engaged drug reprofiling or drug repurposing to recognize possible inhibitors of protease protein 6M03 in an instantaneous approach through computational docking studies. RESULTS: We screened 16 FDA-approved anti-viral drugs that were known for different viral infections to be tested against this contagious novel strain. Through these reprofiling studies, we come up with 5 drugs, namely, Delavirdine, Fosamprenavir, Imiquimod, Stavudine, and Zanamivir, showing excellent results with the negative binding energies in Kcal/mol as - 8.5, - 7.0, - 6.8, - 6.8, and - 6.6, respectively, in the best binding posture. In silico studies allowed us to demonstrate the potential role of these drugs against COVID-19. CONCLUSION: In our study, we also observed the nucleotide sequence of protease protein consisting of 316 amino acid residues and the influence of these pronouncing drugs over these sequences. The outcome of this research work provides researchers with a track record for carrying out further investigational procedures by applying docking simulations and in vitro and in vivo experimentation with these reprofile drugs so that a better drug can be formulated against coronavirus.

Revealing Melatonin's Mysteries: Receptors, Signaling Pathways, and Therapeutics Applications.

Melatonin (5-methoxy-acetyl tryptamine) is a sleep-inducing hormone, and the pineal gland produces it in response to the circadian clock of darkness. In the body, MT1 and MT2 receptors are mostly found, having an orthosteric pocket and ligand binding determinants. Melatonin acts by binding on melatonin receptors, intracellular proteins, and orphan nuclear receptors. It inhibits adenyl cyclase and activates phospholipase C, resulting in gene expression and an intracellular alteration environment. Melatonin signaling pathways are also associated with other intracellular signaling pathways, i. e., cAMP/PKA and MAPK/ERK pathways. Relative expression of different proteins depends on the coupling profile of G protein, accounting pharmacology of the melatonin receptor bias system, and mediates action in a Gi-dependent manner. It shows antioxidant, antitumor, antiproliferative, and neuroprotective activity. Different types of melatonin agonists have been synthesized for the treatment of sleeping disorders. Researchers have developed therapeutics that target melatonin signaling, which could benefit a wide range of medical conditions. This review focuses on melatonin receptors, pharmacology, and signaling cascades; it aims to provide basic mechanical aspects of the receptor's pharmacology, melatonin's functions in cancer and neurodegenerative diseases, and any treatments and drugs designed for these diseases. This will allow a basic comparison between the receptors in question, highlighting any parallels and differences that may exist and providing fundamental knowledge about these receptors to future researchers.

2-Hydroxybenzohydrazide as a novel potential candidate against nociception, inflammation, and pyrexia: in vitro, in vivo, and computational approaches.

The current study was designed to evaluate the 2-hydroxybenzohydrazide (HBH) as a drug having efficacy against pyrexia, inflammation, and nociception. Besides, the therapeutic effects of HBH on oxidative stress and C-reactive proteins were also evaluated. The pharmacological studies on HBH (20-60 mg/kg) were conducted using nociception, inflammation, and pyrexia standard models. Naloxone antagonism was performed to assess the possible involvement of opioidergic mechanisms. The antioxidant study was conducted on ABTS and DPPH assays using gallic acid as a standard. Moreover, the binding capability of HBH with enzymes cyclooxygenase-I/II (COX-I/II) was determined using molecular modeling analysis. The findings indicated that the HBH dose-dependently inhibited pain, inflammation, and pyrexia. The HBH has significant anti-nociceptive and anti-inflammatory activities at 60 mg/kg (***p < 0.001), similar to the lower doses of diclofenac sodium (50 mg/kg) and tramadol (30 mg/kg). The HBH at 60 mg/kg reduced pyrexia as paracetamol (150 mg/kg). The HBH at 20-60 mg/kg doses declined the plasma C-reactive protein concentration. The mechanistic studies showed that the anti-nociceptive effect of HBH was antagonized by naloxone, indicating that the opioidergic mechanisms are involved. Furthermore, computational studies showed that the HBH exhibited an affinity for COX-I/II target receptors. The HBH significantly inhibited ABTS and DPPH radicals (IC50 = 33.81 and 26.74 µg/ml). These results proposed that the HBH has significant antipyretic, anti-inflammatory, and anti-nociceptive activities involving opioidergic mechanism.

Rh-Catalyzed Annulation of Enaminones with Maleimides for Functionalized Aza-spiro α-Tetralones and Benzo[e]isoindoles via C-H Activation/C═C Bond Cleavage.

An unprecedented strategy for Rh-catalyzed C-H activation/C═C bond cleavage of enaminones is described for the construction of biologically interesting aza-spiro α-tetralones and benzo[e]isoindoles. This protocol provides diversely functionalized aza-spiro α-tetralones and benzo[e]isoindoles in good yields via a [4 + 2] annulation of the exomaleimides and maleimides. This strategy displays a good substrate scope, outstanding functional group tolerance, and excellent regioselectivity.