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The rise of bacterial infections and increasing antibiotic resistance underscores an urgent need for new, effective antimicrobial agents with marine bacteria offering a unique and promising source for novel antibiotic compounds to combat persistent and emerging pathogens. In this research, five compounds were achieved from marine Streptomyces sp., C2-13, and their yield was enhanced with the addition of zinc sulfate at 0.5 mM. All compounds have been evaluated for their antibacterial activity against multiple pathogens, among which good activity was achieved against S. aureus , while potent activity was achieved against Riemerella anatipestifer with its IC50 value at 200 µm and bactericidal effect at 300 µm. Among all compounds, 4 was more active against both pathogens. A transcriptome analysis of active compound 4 showed its antibacterial effect on R. anatipestifer by inhibiting 30S and 50S ribosomal subunits, resistance mechanisms, and gliding motility proteins IX secretion system (T9SS) and interfering with protein translations process, secretion system, defense and resistance mechanisms, ultimately resulting in effective inhibition of normal bacterial growth and its motility. To investigate the anti-bacterial mechanism, all compounds were docked with two enzymes and TLR4 protein for predicting the vaccine construct, and the best docking score was achieved against RMFP with the highest score of -12.9 for compound 4. In silico cloning was carried out to ensure the expression of proteins generated and were cloned using E. coli as a host. The simulation studies have shown that both compound 4–RMFP and TLR4–RMFP complex are stable with the system. To the best of our knowledge, this is the first study investigating marine bacterial metabolites against R. anatipestifer with their anti-bacterial mechanism and enhancing their yield through the addition of zinc sulfate ions. [ABSTRACT FROM AUTHOR]

Neuropathic pain has been characterized as chronic pain resulting from pathological damage to the sensorimotor system. Because of its complex nature, it remains refractory to most of the therapeutic interventions, and surgical intervention and physiotherapy alongside steroidal treatments remain the only treatment protocols with limited success, hence solidifying the need to find efficacious therapeutic alternatives. Emodin was used as a post-treatment for its potential to be neuroprotective in the treatment of chronic constriction injury-induced NP. The first day following surgery, Emodin treatment began, and it lasted until the 21st day. On days 3, 7, 14 and 21, all behavioral investigations were conducted. The sciatic nerve and spinal cord were extracted for further molecular examination. Emodin elevated response latency, was able to delay the onset of mechanical hyperalgesia in rats on days 7, 14, and 21 and reduced the CCI-induced paw deformation. Emodin treatment significantly reduced lipid peroxidation and NO levels while restoring the GST, GSH and catalase. It significantly improved the disorientation of the sciatic nerve and spinal cord confirmed by H & E staining and reduced inflammatory markers as observed by the quantification of COX-2, TNF-α, p-NFκb and up-regulated PPAR-γ levels by ELISA and PCR. According to the findings, Emodin has antinociceptive and anti-hyperalgesic properties, which reduced pain perception and inflammation. We also suggested the involvement of PPAR-γ pathway in the therapeutic potential of emodin in chronic nerve injury. [ABSTRACT FROM AUTHOR]

Evolved over eons to encode biological assays, plants-derived natural products are still the first dawn of drugs. Most researchers have focused on natural compounds derived from commonly used Pimpinella species, such as P. anisum, P. thellungiana, P. saxifrage, and P. brachycarpa, to investigate their antioxidant, antibacterial, and anti-inflammatory properties. Ethnopharmacological studies demonstrated that the genus Pimpinella has the homology characteristics of medicine and food and mainly in the therapy of gastrointestinal dysfunction, respiratory diseases, deworming, and diuresis. The natural product investigation of Pimpinella spp. revealed numerous natural products containing phenylpropanoids, terpenoids, flavonoids, coumarins, sterols, and organic acids. These natural products have the potential to provide future drugs against crucial diseases, such as cancer, hypertension, microbial and insectile infections, and severe inflammations. It is an upcoming field of research to probe a novel and pharmaceutically clinical value on compounds from the genus Pimpinella. In this review, we attempt to summarize the present knowledge on the traditional applications, phytochemistry, and pharmacology of more than twenty-five species of the genus Pimpinella. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD), once considered a rare disease, is now the most common form of dementia in the elderly population. Current drugs (cholinesterase inhibitors and glutamate antagonists) are safe but of limited benefit to most patients, offering symptomatic relief without successful cure of the disease. Since the last several decades, there has been a great need for the development of a treatment that might cure the underlying causes of AD and thereby slow its progression in vulnerable individuals. That is why phase I, II, and III studies that act on several fronts, such as cognitive improvement, symptom reduction, and enhancing the basic biology of AD, are imperative to stop the disease. This review discusses current treatment strategies, summarizing the clinical features and pharmacological properties, along with molecular docking analyses of the existing medications. [ABSTRACT FROM AUTHOR]

The pentacyclic triterpenoids (PTs) of plant origin are reputed to restrain prostate cancer (PCa) cell proliferation. This study aims to assess 3-epifriedelinol (EFD) isolated from aerial part of Ipomoea batatas against PCa and its potential mechanism, in vitro and in vivo. Molecular docking affirms good binding affinity of the compound with target proteins exhibiting binding energy of −7.9 Kcal/mol with BAX, −8.1 Kcal/mol (BCL-2), −1.9 Kcal/mol (NF-κB) and −8.5 Kcal/mol with P53. In the MTT assay, EFD treatment (3–50 µM) showed a significant (p < 0.05 and p < 0.01) dose and time dependent drop in the proliferative graph of DU145 and PC3, and an upsurge in apoptotic cell population. EFD displayed substantial IC50 against DU145 (32.32 ± 3.72 µM) and PC3 (35.22 ± 3.47 µM). According to Western blots, EFD administration significantly enhanced the cleavage of caspases and PARP, elevated BAX and P53 and decreased BCL-2 and NF-κB expression, thereby triggering apoptosis in PCa cells. When male Sprague Dawley rats were intoxicated with Bisphenol A (BPA), an apparent increase in prostate mass (0.478 ± 0.08 g) in comparison to control (0.385 ± 0.03 g) indicates prostatitis. Multidose treatment of EFD (10 mg/kg) significantly reduced prostate size (0.404 ± 0.05 g). EFD exhibited substantial curative potential in vivo, as hematological, hormonal and histopathological parameters have been significantly improved. Reduced peroxidation (TBARS), and suppression of inflammatory markers i.e., NO, IL-6 and TNF-α, signposts substantial antiinflammatory potential of the compound. Overall, EFD has shown better binding affinity with target molecules, acceptable ADMET profile, potent antiproliferative and apoptotic nature and significant reduction in inflamed prostate mass of rats. The present study demonstrates acceptable physicochemical and pharmacokinetic properties of the compound with excellent drugable nature, hence EFD in the form of standardized formulation can be developed as primary or adjuvant therapy against PCa and toxins-induced gonadotoxicity. [ABSTRACT FROM AUTHOR]

Pharmacological strategies to lower the viral load among patients suffering from severe diseases were researched in great detail during the SARS-CoV-2 outbreak. The viral protease Mpro (3CLpro) is necessary for viral replication and is among the main therapeutic targets proposed, thus far. To stop the pandemic from spreading, researchers are working to find more effective Mpro inhibitors against SARS-CoV-2. The 33.8 kDa Mpro protease of SARS-CoV-2, being a nonhuman homologue, has the possibility of being utilized as a therapeutic target against coronaviruses. To develop drug-like compounds capable of preventing the replication of SARS-main CoV-2's protease (Mpro), a computer-aided drug design (CADD) approach is extremely viable. Using MOE, structure-based virtual screening (SBVS) of in-house and commercial databases was carried out using SARS-CoV-2 proteins. The most promising hits obtained during virtual screening (VS) were put through molecular docking with the help of MOE. The virtual screening yielded 3/5 hits (in-house database) and 56/66 hits (commercial databases). Finally, 3/5 hits (in-house database), 3/5 hits (ZINC database), and 2/7 hits (ChemBridge database) were chosen as potent lead compounds using various scaffolds due to their considerable binding affinity with Mpro protein. The outcomes of SBVS were then validated using an analysis based on molecular dynamics simulation (MDS). The complexes' stability was tested using MDS and post-MDS. The most promising candidates were found to exhibit a high capacity for fitting into the protein-binding pocket and interacting with the catalytic dyad. At least one of the scaffolds selected will possibly prove useful for future research. However, further scientific confirmation in the form of preclinical and clinical research is required before implementation. [ABSTRACT FROM AUTHOR]

Diseases affecting the brain and spinal cord fall under the umbrella term "central nervous system disease". Most medications used to treat or prevent chronic diseases of the central nervous system cannot cross the blood–brain barrier (BBB) and hence cannot reach their intended target. Exosomes facilitate cellular material movement and signal transmission. Exosomes can pass the blood–brain barrier because of their tiny size, high delivery efficiency, minimal immunogenicity, and good biocompatibility. They enter brain endothelial cells via normal endocytosis and reverse endocytosis. Exosome bioengineering may be a method to produce consistent and repeatable isolation for clinical usage. Because of their tiny size, stable composition, non-immunogenicity, non-toxicity, and capacity to carry a wide range of substances, exosomes are indispensable transporters for targeted drug administration. Bioengineering has the potential to improve these aspects of exosomes significantly. Future research into exosome vectors must focus on redesigning the membrane to produce vesicles with targeting abilities to increase exosome targeting. To better understand exosomes and their potential as therapeutic vectors for central nervous system diseases, this article explores their basic biological properties, engineering modifications, and promising applications. [ABSTRACT FROM AUTHOR]

Low temperatures have a negative effect on plant development. Plants that are exposed to cold temperatures undergo a cascade of physiological, biochemical, and molecular changes that activate several genes, transcription factors, and regulatory pathways. In this review, the physiological, biochemical, and molecular mechanisms of Camellia sinensis have been discussed. Calmodulin binding transcription activator (CAMTAs) by molecular means including transcription is one of the novel genes for plants' adaptation to different abiotic stresses, including low temperatures. Therefore, the role of CAMTAs in different plants has been discussed. The number of CAMTAs genes discussed here are playing a significant role in plants' adaptation to abiotic stress. The illustrated diagrams representing the mode of action of calcium (Ca2+) with CAMTAs have also been discussed. In short, Ca2+ channels or Ca2+ pumps trigger and induce the Ca2+ signatures in plant cells during abiotic stressors, including low temperatures. Ca2+ signatures act with CAMTAs in plant cells and are ultimately decoded by Ca2+sensors. To the best of our knowledge, this is the first review reporting CAMAT's current progress and potential role in C. sinensis, and this study opens a new road for researchers adapting tea plants to abiotic stress. [ABSTRACT FROM AUTHOR]

Increased environmental pollution, urbanization, and a wide variety of anthropogenic activities have led to the release of toxic pollutants into the environment, including heavy metals (HMs). It has been found that increasing concentrations of HMs lead to toxicity, mineral imbalances, and serious diseases, which are occurring more and more frequently. Therefore, testing has become imperative to detect these deficiencies in a timely manner. The detection of traces of HMs, especially toxic ones, in human tissues, various biological fluids, or hair is a complex, high-precision analysis that enables early diagnosis, addressing people under constant stress or exposed to a toxic environment; the test also targets people who have died in suspicious circumstances. Tissue mineral analysis (TMA) determines the concentration of toxic minerals/metals at the intracellular level and can therefore determine correlations between measured concentrations and imbalances in the body. Framing the already-published information on the topic, this review aimed to explore the toxicity of HMs to human health, the harmful effects of their accumulation, the advantages vs. the disadvantages of choosing different biological fluids/tissues/organs necessary for the quantitative measurement of HM in the human body, as well as the choice of the optimal method, correlated with the purpose of the analysis. [ABSTRACT FROM AUTHOR]

Brucella suis, one of the causative agents of brucellosis, is Gram-negative intracellular bacteria that may be found all over the globe and it is a significant facultative zoonotic pathogen found in livestock. It may adapt to a phagocytic environment, reproduce, and develop resistance to harmful environments inside host cells, which is a crucial part of the Brucella life cycle making it a worldwide menace. The molecular underpinnings of Brucella pathogenicity have been substantially elucidated due to comprehensive methods such as proteomics. Therefore, we aim to explore the complete Brucella suis proteome to prioritize the novel proteins as drug targets via subtractive proteo-genomics analysis, an effort to conjecture the existence of distinct pathways in the development of brucellosis. Consequently, 38 unique metabolic pathways having 503 proteins were observed while among these 503 proteins, the non-homologs (n = 421), essential (n = 350), drug-like (n = 114), virulence (n = 45), resistance (n = 42), and unique to pathogen proteins were retrieved from Brucella suis. The applied subsequent hierarchical shortlisting resulted in a protein, i.e., isocitrate lyase, that may act as potential drug target, which was finalized after the extensive literature survey. The interacting partners for these shortlisted drug targets were identified through the STRING database. Moreover, structure-based studies were also performed on isocitrate lyase to further analyze its function. For that purpose, ~18,000 ZINC compounds were screened to identify new potent drug candidates against isocitrate lyase for brucellosis. It resulted in the shortlisting of six compounds, i.e., ZINC95543764, ZINC02688148, ZINC20115475, ZINC04232055, ZINC04231816, and ZINC04259566 that potentially inhibit isocitrate lyase. However, the ADMET profiling showed that all compounds fulfill ADMET properties except for ZINC20115475 showing positive Ames activity; whereas, ZINC02688148, ZINC04259566, ZINC04232055, and ZINC04231816 showed hepatoxicity while all compounds were observed to have no skin sensitization. In light of these parameters, we recommend ZINC95543764 compound for further experimental studies. According to the present research, which uses subtractive genomics, proteins that might serve as therapeutic targets and potential lead options for eradicating brucellosis have been narrowed down. [ABSTRACT FROM AUTHOR]

Saponins are triterpenoid or steroidal glycosides and are an important group of naturally occurring compounds of plant origin. They exhibit diverse pharmacological potentials including radical scavenging, as well as neuroprotective, anti-diabetic and anti-inflammatory activities, owing to their diverse chemical scaffolds. Saponins consist of an aglycone part (non-sugar) and a glycone part (sugar) and have at least one glycosidic (C–O sugar bond) linkage present between the glycone and aglycone mostly at C-3. On the basis of the aglycone part, saponins are classified into triterpenoid glycosides, steroid glycosides and alkaloid glycosides. Saponins exhibit neuroprotective activities against various disorders of the central nervous system (CNS) including stroke, Alzheimer's disease (AD), Huntington's disease (HD) and Parkinson's disease (PD). They mediate their therapeutic effects by modulation of various pathological targets. This study highlights various neuroprotective mechanisms of saponins including free radical scavenging, modulation of neuroprotective signaling pathways, activation of neurotrophic factors, modulation of neurotransmitters, inhibition of BACE1 enzyme and tau hyper-phosphorylation. The study concludes that saponins have considerable efficacy against various pathological targets of neurological disorders, especially AD, and might be an important source of leads against neurodegenerative disorders. [ABSTRACT FROM AUTHOR]

Cancer is one of the most challenging diseases in the modern era for the researchers and investigators. Extensive research worldwide is underway to find novel therapeutics for prevention and treatment of diseases. The extracted natural sources have shown to be one of the best and effective treatments for cell proliferation and angiogenesis. Different approaches including disc potato model, brine shrimp, and chorioallantoic membrane (CAM) assay were adopted to analyze the anticancer effects. Habenaria digitata was also evaluated for MTT activity against NIH/3T3 cell line. The dexamethasone, etoposide, and vincristine sulfate were used as a positive control in these assays. All of the extracts including crude extracts (Hd.Cr), saponin (Hd.Sp), n-hexane (Hd.Hx), chloroform (Hd.Chf), ethyl acetate (Hd.EA), and aqueous fraction (Hd.Aq) were shown excellent results by using various assays. For example, saponin and chloroform have displayed decent antitumor and angiogenic activity by using potato tumor assay. The saponin fraction and chloroform were shown to be the most efficient in potato tumor experiment, demonstrating 87.5 and 93.7% tumor suppression at concentration of 1000 μg/ml, respectively, with IC50 values of 25.5 and 18.3 μg/ml. Additionally, the two samples, chloroform and saponins, outperformed the rest of the test samples in terms of antiangiogenic activity, with IC50 28.63 μg/ml and 16.20 μg/ml, respectively. In characterizing all solvent fractions, the chloroform (Hd.Chf) and saponin (Hd.Sp) appeared to display good effectiveness against tumor and angiogenesis but very minimal activity against A. tumefaciens. The Hd.Chf and Hd.Sp have been prospective candidates in the isolation of natural products with antineoplastic properties. [ABSTRACT FROM AUTHOR]

Drought stress has been shown to have harmful effects on crop productivity worldwide, including in Pakistan, due to rapid climate change scenarios. Extensive work has been reported on the influential role of melatonin (MEL) in either foliar or seed-primed applications; however, its role in root application is seldom reported. We investigated plant biochemical responses, including anti-oxidants, plant pigments, leaf water characteristics, and maize crop production, with MEL treatment under mild and severe drought stress. Maize Cvar. Jalal was subjected to drought stress (60% and 80% of full irrigation) at the four-leaf stage, and MEL was applied as pretreatment with irrigation water at different doses (0, 100, and 200µM). The findings of the study revealed that the Chl a, b, and a + b contents and the carotenoid content significantly increased with MEL application during severe and mild drought stress. After applying 200 µM MEL, leaf water attributes, comprising relative water content (RWC), leaf water content (LWC), and relative saturation deficit (RSD), increased by 1.9%, 100%, and 71.2%, respectively, during mild drought and 17%, 133%, and 32% under severe drought. The anti-oxidant activities of POD, CAT, and APX were remarkably enhanced with MEL during drought stress. Our results showed that root application of 200 µM melatonin boosted seed yield and water productivity by 31% and 38%, and plant biomass increased by 32% and 29% under mild and severe drought stressors compared to plants with no MEL, leading to increased drought tolerance. [ABSTRACT FROM AUTHOR]

Fluorescent molecules absorb photons of specific wavelengths and emit a longer wavelength photon within nanoseconds. Recently, fluorescent materials have been widely used in the life and material sciences. Fluorescently labelled heterocyclic compounds are useful in bioanalytical applications, including in vivo imaging, high throughput screening, diagnostics, and light-emitting diodes. These compounds have various therapeutic properties, including antifungal, antitumor, antimalarial, anti-inflammatory, and analgesic activities. Different neutral fluorescent markers containing nitrogen heterocycles (quinolones, azafluoranthenes, pyrazoloquinolines, etc.) have several electrochemical, biological, and nonlinear optic applications. Photodynamic therapy (PDT), which destroys tumors and keeps normal tissues safe, works in the presence of molecular oxygen with light and a photosensitizing drugs (dye) to obtain a therapeutic effect. These compounds can potentially be effective templates for producing devices used in biological research. Blending crown compounds with fluorescent residues to create sensors has been frequently investigated. Florescent heterocyclic compounds (crown ether) increase metal solubility in non-aqueous fluids, broadening the application window. Fluorescent supramolecular polymers have widespread use in fluorescent materials, fluorescence probing, data storage, bio-imaging, drug administration, reproduction, biocatalysis, and cancer treatment. The employment of fluorophores, including organic chromophores and crown ethers, which have high selectivity, sensitivity, and stability constants, opens up new avenues for research. Fluorescent organic compounds are gaining importance in the biological world daily because of their diverse functionality with remarkable structural features and positive properties in the fields of medicine, photochemistry, and spectroscopy. [ABSTRACT FROM AUTHOR]

Although, quantum dots (QDs) of two-dimensional (2D) molybdenum disulfide (MoS2) have shown great potential for various applications, such as sensing, catalysis, energy storage, and electronics. However, the lack of a simple, scalable, and inexpensive fabrication method for QDs is still a challenge. To overcome this challenge, a lot of attention has been given to the fabrication of QDs, and several fabrication strategies have been established. These exfoliation processes are mainly divided into two categories, the 'top-down' and 'bottom-up' methods. In this review, we have discussed different top-down exfoliation methods used for the fabrication of MoS2 QDs and the advantages and limitations of these methods. A detailed description of the various properties of QDs is also presented. [ABSTRACT FROM AUTHOR]

Simple Summary: The most well-known oncogene and one with the highest rates of mutation across all cancers is K-Ras, also known as the Kirsten rat sarcoma viral oncogene homologue. It is also linked to certain cancers with a high mortality rate, including pancreatic ductal adenocarcinoma (PDAC), non-small-cell lung cancer (NSCLC), and colorectal cancer (CRC). The aim of this study was to make peptides that inhibit K-Ras G12V by computer-aided drug design methods. Our results showed that the top four selected peptides interact with K-Ras more strongly than the reference-peptide and can stop K-Ras from activating. Our binding affinity analyses demonstrated that the developed peptides can inhibit K-Ras and slow cancer growth. Ras plays a pivotal function in cell proliferation and is an important protein in signal transduction pathways. Mutations in genes encoding the Ras protein drive the signaling cascades essential for malignant transformation, tumour angiogenesis, and metastasis and are responsible for above 30% of all human cancers. There is evidence that N-Ras, K-Ras, and H-Ras play significant roles in human cancer. The mutated K-Ras protein is typically observed in malignant growths. Mutant K-Ras is the most common in lung, colon, and pancreatic cancers. The purpose of this research was to create peptides that inhibit K-Ras G12V. The crystal structure of the mutant K-Ras G12V-H-REV107 complex was obtained from a protein data bank. Further, we used a residue scan approach to create unique peptides from the reference peptide (H-REV107). AMBER molecular dynamics simulations were used to test the stability of the top four proposed peptides (based on binding free energies). Our findings showed that the top four selected peptides had stronger interactions with K-Ras than the reference peptide and have the ability to block the activation function of K-Ras. Our extensive analyses of binding affinities showed that our designed peptide possesses the potential to inhibit K-Ras and to reduce the progression of cancer. [ABSTRACT FROM AUTHOR]

Mandelic acid is a valuable chemical that is commonly used in the synthesis of various drugs, in antibacterial products, and as a skin care agent in cosmetics. As it is an important chemical, various methods are used to synthesize and extract this compound. However, the yields of the used processes is not significant. A dilute aqueous solution is obtained when using several production methods, such as a fermentation, etc. In this study, the reactive extraction of mandelic acid from aqueous solutions using tri-n-octylamine extractant at 298.15 K was investigated. Dimethyl phthalate (DMP), methyl isobutyl ketone (MIBK), 2-octanone, 1-octanol, n-pentane, octyl acetate, and toluene were used as diluents. The batch extraction results of the mandelic acid experiments were obtained for the development of a process design. Calculations of the loading factor (Z), distribution coefficient (D), and extraction efficiency (E%) were based on the experimental data. The highest separation yield was obtained as 98.13% for 0.458 mol.L−1 of tri-n-octylamine concentration in DMP. The overall extraction constants were analyzed for the complex of acid-amine by the Bizek approach, including K11, K12, and K23. [ABSTRACT FROM AUTHOR]

This present study aimed to delineate Rumex hastatus D. Don crude extract (Rh.Cr), n-Hexane, ethyl acetate, aqueous fractions (Rh.n-Hex, Rh.ETAC, Rh.Aq) and rutin for antidiarrheal, antisecretory effects, anti-spasmodic, gastrointestinal transient time, anti H. pylori, antiulcer effects, and toxicology. The preliminary phytochemical analysis of Rumex hastatus showed different phytoconstituents and shows different peaks in GC-MC chromatogram. Rumex hastatus crude extract (Rh.Cr), fractions, and rutin attributed dose-dependent (50–300 mg/kg) protection (0–100%) against castor oil-induced diarrhea and dose-dependently inhibited intestinal fluid secretions in mice. They decreased the distance traversed by charcoal in the gastrointestinal transit model in rats. In rabbit jejunum preparations, Rh.Cr and Rh.ETAC caused a concentration-dependent relaxation of both spontaneous and K+ (80 mM)-induced contractions at a similar concentration range, whereas Rh.n-Hex, rutin, and verapamil were relatively potent against K+-induced contractions and shifted the Ca2+ concentration–response curves (CRCs) to the right, Rh.Cr (0.3–1 mg/mL) and Rh.ETAC (0.1–0.3 mg/mL) shifted the isoprenaline-induced inhibitory CRCs to the left. Rh.n-Hex, Rh.ETAC and rutin showed anti-H. pylori effect, also shows an inhibitory effect against H+/K+-ATPase. Rumex hastatus showed gastroprotective and antioxidant effects. Histopathological evaluation showed improvement in cellular architecture and a decrease in the expression of inflammatory markers such as, cyclooxygenase (COX-2), tumor necrosis factor (TN,F-α) and phosphorylated nuclear factor kappa B (p-NFƙB), validated through immunohistochemistry and ELISA techniques. In RT-PCR it decreases H+/K+-ATPase mRNA levels. Rumex hastatus was found to be safe to consume up to a dose of 2000 mg/kg in a comprehensive toxicity profile. Docking studies revealed that rutin against H+/K+-ATPase pump and voltage-gated L-type calcium channel showed E-values of −8.7 and −9.4 Kcal/mol, respectively. MD simulations Molecular Mechanics Poisson Boltzmann surface area and molecular mechanics Generalized Born surface area (MMPBSA/GBSA) findings are consistent with the in-vitro, in-vivo and docking results. [ABSTRACT FROM AUTHOR]

The current work examined the pharmacological potential of a selected flavanone derivative 2-hydroxyflavanone as a promising remedy for the treatment and management of pain. The selected flavanone derivative (2-HF) was evaluated for its analgesic and anti-inflammatory potentials following standard pharmacological protocols including hot plate, acetic acid-induced writhing and tail immersion tests. Naloxone and pentylenetetrazol were used to evaluate the potential implication of GABAergic and opioidergic mechanisms. The anti-inflammatory potential of 2-HF was confirmed using carrageenan-, serotonin- and histamine-induced paw edema models as well as a xylene-induced ear edema model. Furthermore, the anti-neuropathic potential of 2-HF was tested using a cisplatin-induced neuropathic pain model. Our sample, at the tested concentrations of 15, 30 and 45 mg kg−1, showed considerable analgesic, anti-inflammatory effects, as well as efficacy against neuropathic pain. Naloxone and pentylenetetrazol at 1 and 15 mg kg−1 antagonized the anti-nociceptive activities of 2-hydroxyflavanone indicating the involvement of opioidergic and GABAergic mechanisms. In the static allodynia model, combination of gabapentin 75 mg kg−1 with 2-HF at 15, 30, 45 mg kg−1 doses exhibited considerable efficacy. In cold allodynia, 2-hydroxyflavanone, at doses of 15, 30 and 45 mg kg−1 and in combination with gabapentin (75 mg kg−1), demonstrated prominent anti-allodynic effects. The paw withdrawal latency was considerably increased in gabapentin + cisplatin treated groups. Moreover, cisplatin + 2-hydroxyflavanone 15, 30, 45 mg kg−1 showed increases in paw withdrawal latency. Likewise, considerable efficacy was observed for 2-hydroxyflavanone in thermal hyperalgesia and dynamic allodynia models. Our findings suggest that 2-hydroxyflavanone is a potential remedy for pain syndrome, possibly mediated through opioidergic and GABAergic mechanisms. [ABSTRACT FROM AUTHOR]

Isoxazole derivatives are significant enough due to their wide range of pharmacological and therapeutic activities. The purpose of the current study is to use computational, in vitro, in vivo, and extensive molecular approaches to examine the possible anti-ulcer activity of 4-benzylidene-3 methyl-1,2-isoxazol-5(4H)-one (MBO). Biovia Discovery Studio visualizer (DSV) was utilized for virtual screening. A tissue antioxidant investigation, H+/K+-ATPase test, and anti-H. pylori activities were carried out. ELISA, immunohistochemistry, and PCR methods were employed for the proteome analysis. An ethanol-induced stomach ulcer model was used to examine the anti-ulcer potential in rats. The binding affinities for MBO ranged from −5.4 to −8.2 Kcal/mol. In vitro findings revealed inhibitory activity against H. pylori and the H+/K+-ATPase pump. It also enhanced levels of glutathione, catalase, and glutathione-S-transferase and reduced lipid peroxidation levels in gastric tissues of rats. In vivo results showed the gastro-protective effect of MBO (30 mg/kg) in ulcerative rat stomachs. The proteomic study revealed decreased expression of inflammatory markers (cyclooxygenase-2, p-NFkB, and TNF-α). In RT-PCR analysis, the expression levels of H+/K+-ATPase were reduced. Furthermore, ADMET (absorption, distribution, metabolism, excretion and toxicity) studies revealed that MBO has high GIT solubility and has a safer profile for cardiac toxicity. This study suggests that MBO displayed anti-ulcer potential, which may have been mediated through the inhibition of the H+/K+-ATPase pump, as well as antioxidant and anti-inflammatory pathways. It has the potential to be a lead molecule in the treatment of peptic ulcers with fewer adverse effects. [ABSTRACT FROM AUTHOR]

Indigofera linifolia is a medicinally important plant, and by virtue of its rich phytochemical composition, this plant is widely used as essential component in traditional medication systems. Due to its wide range of medicinal applications, the extract-loaded chitosan (Ext+Ch), extract-loaded PEG (Ext+PEG), and extract-loaded locust bean gum (Ext+LGB) nanoparticles (NPs) were prepared in the present study. The prepared NPs were then evaluated for their antibacterial, antioxidant, and antidiabetic potentials. Antibacterial activities of the crude extract and the synthesized NPs were performed following standard procedures reported in the literature. The antioxidant capabilities of extract and NPs were evaluated using DPPH free radical scavenging assay. The antidiabetic potential of the samples was evaluated against α-amylase and α-glucosidase. Ext+PEG NPs showed more potent antibacterial activity against the selected strains of bacteria with the highest activity against Escherichia coli. The lowest antibacterial potential was observed for Ext+LGB NPs. The Ext+LGB NPs IC50 value of 39 μg/mL was found to be the most potent inhibitor of DPPH free radicals. Ext+LGB NPs showed a greater extent of inhibition against α-glucosidase and α-amylase with an IC50 of 83 and 78 μg/mL, whereas for the standard acarbose the IC50 values recorded against the mentioned enzymes were 69 and 74 μg/mL, respectively. A high concentration of phenolics and flavonoids in the crude extract was confirmed through TPC and TFC tests, HPLC profiling, and GC–MS analysis. It was considered that the observed antibacterial, antidiabetic, and antioxidant potential might be due the presence of these phenolics and flavonoids detected. The plant could thus be considered as a potential candidate to be used as a remedy of the mentioned health complications. However, further research in this regard is needed to isolate the exact responsible compounds of the observed biological potentials exhibited by the crude extract. Further, toxicity and pharmacological evaluations in animal models are also needed to establish the safety or toxicity profile of the plant. [ABSTRACT FROM AUTHOR]

Three undescribed guaiane-type sesquiterpenes (1–3), and a monoterpenoid (4) along with eleven known compounds (5 − 15) were isolated from the crude extract of Litsea lancilimba Merr. The structures of all the isolated compounds were extensively elucidated on the basis of comprehensive spectroscopic techniques (HRESIMS, 1 D NMR, and 2 D NMR). Their relative and absolute configurations were comprehensively established by NOESY spectroscopy, circular dichroism (ECD) and the calculated ECD analysis. All the isolates were tested for anti-inflammatory activity by measuring the amount of nitric oxide production. Amongst tested compounds, compounds 1 − 3 exhibited moderate inhibitory activities against the production of nitric oxide with IC50 value of 35.5, 32.1, 46.7 μM in RAW264.7 cells stimulated by LPS, respectively. [ABSTRACT FROM AUTHOR]

Scutellaria (Lamiaceae) comprises over 360 species. Based on its morphological structure of calyx, also known as Skullcap, it is herbaceous by habit and cosmopolitan by habitat. The species of Scutellaria are widely used in local communities as a natural remedy. The genus contributed over three hundred bioactive compounds mainly represented by flavonoids and phenols, chemical ingredients which serve as potential candidates for the therapy of various biological activities. Thus, the current review is an attempt to highlight the biological significance and its correlation to various isolated bioactive ingredients including flavonoids, terpenoids, phenols, alkaloids, and steroids. However, flavonoids were the dominant group observed. The findings of the Scutellaria reveal that due to its affluent basis of numerous chemical ingredients it has a diverse range of pharmacological potentials, such as antimicrobial, antioxidant, antifeedant, enzyme inhibition, anti-inflammatory, and analgesic significance. Currently, various bioactive ingredients have been investigated for various biological activities from the genus Scutellaria in vitro and in vivo. Furthermore, these data help us to highlight its biomedical application and to isolate the responsible compounds to produce innovative medications as an alternative to synthetic drugs. [ABSTRACT FROM AUTHOR]

In the current study, a series of new (2S,3S)-2-(4-isopropylbenzyl)-2-methyl-4-nitro-3-phenylbutanals (FM1-6) with their corresponding carboxylic acid analogues (FM7-12) has been synthesized. Initially, the aldehydic derivatives were isolated in the diastereomeric form, and the structures were confirmed with NMR, MS and elemental analysis. Based on the encouraging results in in vitro COX 1/2, 5-LOX and antioxidant assays, we oxidized the compounds and obtained the pure single (major) diastereomer for activities. Among all the compounds, FM4, FM10 and FM12 were the leading compounds based on their potent IC50 values. The IC50 values of compounds FM4, FM10 and FM12 were 0.74, 0.69 and 0.18 µM, respectively, in COX-2 assay. Similarly, the IC50 values of these three compounds were also dominant in COX-1 assay. In 5-LOX assay, the majority of our compounds were potent inhibitors of the enzyme. Based on the potency and safety profiles, FM10 and FM12 were subjected to the in vivo experiments. The compounds FM10 and FM12 were observed with encouraging results in in vivo analgesic and anti-inflammatory models. The molecular docking studies of the selected compounds show binding interactions in the minimized pocked of the target proteins. It is obvious from the overall results that FM10 and FM12 are potent analgesic and anti-inflammatory agents. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is the most common cancer in men, accounting for approximately 10% of all new cases in the United States. Plant-derived bioactive compounds, such as pentacyclic triterpenoids (PTs), have the ability to inhibit PCa cell proliferation. We isolated and characterized nummularic acid (NA), a potent PT, as a major chemical constituent of Ipomoea batatas, a medicinal food plant used in ethnomedicine for centuries. In the current study, in vitro antiproliferative potential against PCa cells (DU145 and PC3) via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay; Western blot protein expression analysis; absorption, distribution, metabolism, excretion (ADME); pharmacokinetic prediction studies; and bisphenol A (BPA)-induced prostate inhibition in Sprague Dawley rats were conducted to gauge the anti-cancer ability of NA. Significant (p < 0.05 and p < 0.01) time- and dose-dependent reductions in proliferation of PCa cells, reduced migration, invasion, and increased apoptotic cell population were recorded after NA treatment (3–50 µM). After 72 h of treatment, NA displayed significant IC50 of 21.18 ± 3.43 µM against DU145 and 24.21 ± 3.38 µM against PC3 cells in comparison to the controls cabazitaxel (9.56 ± 1.45 µM and 12.78 ± 2.67 µM) and doxorubicin (10.98 ± 2.71 µM and 15.97 ± 2.77 µM). Further deep mechanistic studies reveal that NA treatment considerably increased the cleavage of caspases and downstream PARP, upregulated BAX and P53, and downregulated BCL-2 and NF-κB, inducing apoptosis in PCa cells. Pharmacokinetic and ADME characterization indicate that NA has a favorable physicochemical nature, with high gastrointestinal absorption, low blood–brain barrier permeability, no hepatotoxicity, and cytochrome inhibition. BPA-induced perturbations of prostate glands in Sprague Dawley rats show a potential increase (0.478 ± 0.28 g) in prostate weight compared to the control (0.385 ± 0.13 g). Multi-dose treatment with NA (10 mg/kg) significantly reduced the prostate size (0.409 ± 0.21 g) in comparison to the control. NA-treated groups exhibited substantial restoration of hematological and histological parameters, reinstatement of serum hormones, and suppression of inflammatory markers. This multifaceted analysis suggests that NA, as a novel small molecule with a strong pharmacokinetic and pharmacological profile, has the potential to induce apoptosis and death in PCa cells. [ABSTRACT FROM AUTHOR]

Ferroptosis is a recently described programmed cell death mechanism that is characterized by the buildup of iron (Fe)-dependent lipid peroxides in cells and is morphologically, biochemically, and genetically distinct from other forms of cell death, having emerged to play an important role in cancer biology. Ferroptosis has significant importance during cancer treatment because of the combination of factors, including suppression of the glutathione peroxidase 4 (Gpx4), cysteine deficiency, and arachidonoyl (AA) peroxidation, which cause cells to undergo ferroptosis. However, the physiological significance of ferroptosis throughout development is still not fully understood. This current review is focused on the factors and molecular mechanisms with the diagrammatic illustrations of ferroptosis that have a role in the initiation and sensitivity of ferroptosis in various malignancies. This knowledge will open a new road for research in oncology and cancer management. [ABSTRACT FROM AUTHOR]

This Special Issue includes many high advanced quality papers that focus on natural products with their potent pharmacological potential targeting various areas of diseases. The results revealed that two compounds have potent anti-inflammatory activity in vitro against COX ½ and 5-LOX, antioxidant activity against DPPH free radicals and in vivo analgesic activity. The papers in this Special Issue present new insights into natural products with potent anticancer, anti-inflammatory, antioxidant, anti-bacterial, analgesic, anti-diabetic, and enzyme inhibitory activities. [Extracted from the article]

Objectives: To determine the frequency of spontaneous closure of postoperative enterocutaneous fistula at a tertiary care hospital. Study Design: Descriptive Case Series. Setting: Department of General Surgery Unit-I, Nishtar Medical University/ Hospital, Multan. Period: Nine months 1/4/2018 to 31/12/2018. Material & Methods: Non-probability consecutive sampling. Results: From 80 patients, 34 (42.5%) were male and 46 (57.5%) were female. Mean age of our patients was 40.31 ± 10.58 years. Most of our patients i.e. 55 (68.8%) belonged to poor families. Mean body mass index of our patients was 24.67 ± 3.39 kg/m2 and obesity was present in only 14 (17.5%) patients. Initial surgery was elective in 53 (66.2%) and emergency surgery in 27 (33.8%) patients. Site of origin of ECFs was gastric in 17 (21.3%), duodenum in 22 (27.5%), Jejunum in 14 (17.4%), Ilium was involved in 17(21.3%) and colorectal in 10(12.5%). Mean disease duration was 3.21 ± 2.09 weeks and mean duration of surgery was noted to be 4.71 ± 2.13 hours and 73.8% underwent surgical procedure for up to 5 hours. Mean hospital stay was noted to be 13.58 ± 7.41 days while 73.8% stayed in hospital for more than 7 days. Spontaneous closure of post-operative enterocutaneous fistula was noted in 25 (31.3%) of our patients. Conclusion: Spontaneous closure of post-operative enterocutaneous fistula without any surgical intervention is quite common. [ABSTRACT FROM AUTHOR]

The article titled "Potential Role of Natural Products to Combat Radiotherapy and Their Future Perspectives" has been retracted due to significant overlap with a previously published review. The editorial office conducted an investigation and confirmed the similarities, leading to the decision to retract the article. The retraction was approved by the Editor-in-Chief of the journal Molecules, and the authors agree with this decision. [Extracted from the article]

Guaiane-type sesquiterpenoids are most prevalent in the genus Cinnamomum. Hence this study investigates the structures, anti-nociceptive and IL-6 targeted anti-inflammatory potential of three novels C-14 guaiane-type sesquiterpenoids and two new monoterpenoids, isolated from Cinnamomum migao. The structures were precisely confirmed and characterized through the modern chromatographic and spectroscopic techniques of HRESIMS, 1D NMR, 2D NMR, experimental circular dichroism (ECD), and calculated (ECD). Novel sesquiterpenoids 1 and 2 exhibited significant anti-inflammatory activities against the NO production and pro-inflammatory cytokines. Their IC 50 values were determined as 9.52 and 13.42 μΜ against IL-6 mRNA, respectively. Similarly, subcutaneous injection of n -BuT and EA extracts showed a dose-dependent suppression of formalin-induced tonic biting/licking responses during the tonic antinociceptive phase. Furthermore, absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis of guaiane-type sesquiterpenoids 1 and 2 displayed that both compounds have a high level of GIT absorption, with a high zone of safety for cardiac and hepatotoxicity and no inhibition of cytochromes. In addition, molecular docking and simulation studies strengthen the anti-inflammatory potential of sesquiterpene 2 which showed a good binding affinity with IL-6 protein. Overall the inclusive results showed that the extracts and newly isolated guaiane-type sesquiterpenoids from C. migao will provide new evidence for the traditional use of this species to treat inflammation and nociception. [Display omitted] • Three unusual undescribed guaiane-type sesquiterpenoids and two undescribed monoterpenoids were isolated from C. migao. • These compounds were assessed for anti-inflammatory activities against NO production and against pro-inflammatory cytokines. • The ADMET, molecular docking and molecular dynamic simulations studies were also conducted. • The EA, n -BuT extracts and compounds were tested for analgesic properties in formalin-induced anti-nociceptive effect. [ABSTRACT FROM AUTHOR]

Biologically active natural products are spontaneous medicinal entrants, which encourage synthetic access for enhancing and supporting drug discovery and development. Marine bioactive peptides are considered as a rich source of natural products that may provide long-term health, in addition to many prophylactic and curative medicinal drug treatments. The large literature concerning marine peptides has been collected, which shows high potential of nutraceutical and therapeutic efficacy encompassing wide spectra of bioactivities against a number of infection-causing agents. Their antimicrobial, antimalarial, antitumor, antiviral, and cardioprotective actions have achieved the attention of the pharmaceutical industry toward new design of drug formulations, for treatment and prevention of several infections. However, the mechanism of action of many peptide molecules has been still untapped. So in this regard, this paper reviews several peptide compounds by which they interfere with human pathogenesis. This knowledge is one of the key tools to be understood especially for the biotransformation of biomolecules into targeted medicines. The fact that different diseases have the capability to fight at different sites inside the body can lead to a new wave of increasing the chances to produce targeted medicines. [ABSTRACT FROM AUTHOR]