Pharmacology
Association of Anti-TPO Antibody and Inflammatory Markers with Thyroid Ultrasound Findings
The objective of this study was to evaluate the demographic clinical laboratory and ultrasonographic characteristics of patients diagnosed with subclinical hypothyroidism with a particular emphasis on the anti-thyroid peroxidase (anti-TPO) antibody and inflammatory biomarkers.
The study included 157 patients diagnosed with subclinical hypothyroidism categorised into anti-TPO-positive and anti-TPO-negative groups. A retrospective comprehensive evaluation comprising demographic data thyroid medication status ultrasonographic characteristics and laboratory parameters was conducted and statistically analysed between the groups.
Of 157 patients 48.4% were anti-TPO positive. This group was significantly associated with increased levothyroxine (LT4) use and sonographic parenchymal heterogeneity. However there were no significant differences in nodule presence number size or structure. A positive correlation was found between anti-TPO and ferritin levels. In addition a positive correlation was observed between the thyroid-stimulating hormone (TSH)/free T4 ratio and the solidity of nodules as well as between TSH and the neutrophil-to-lymphocyte ratio (NLR). Surprisingly a negative correlation was found between anti-TPO levels and the number of nodules as well as the cystic characterisation of the nodules.
In our study higher levels of anti-TPO and TSH were associated with inflammatory markers such as ferritin and NLR suggesting a possible link with systemic inflammation. Furthermore anti-TPO and the TSH/T4 ratio also showed associations with specific sonographic features of the thyroid gland.
TSH and anti-TPO levels might be associated with systemic inflammation and thyroid sonographic findings in patients with subclinical hypothyroidism. More studies on larger patient populations should confirm the same results to suggest their clinical significance.
Unveiling Promising PARP12 Inhibitors through Virtual Screening for Cancer Therapy
Poly (ADP-ribose) polymerase 12 (PARP12) plays a crucial role in DNA damage response (DDR) through DNA repair maintaining genomic stability. Mutations in PARP12 contribute to genomic instability leading to cancer progression. Targeting PARP12 mutants with small molecule inhibitors offers a promising therapeutic strategy.
This study aims to identify potent inhibitors for PARP12 mutants using molecular docking-based virtual screening from the National Cancer Institute (NCI) compound library followed by molecular dynamics (MD) simulations to validate binding stability.
Homology models of human PARP12 mutants were developed for virtual screening. The top-scoring compounds were refined through molecular docking and their stability was analyzed using all-atomistic MD simulations. Binding free energy (MMGBSA) calculations and structural dynamics assessments including RMSD RMSF RoG and SASA were conducted to evaluate the drug-receptor interactions.
Three promising inhibitors NCI-32743 NCI-32982 and NCI-659779 demonstrated high binding affinity and stability with PARP12 mutants. These compounds showed significant inhibitory potential maintaining strong interactions with the target protein throughout the simulation period. ADMET and pharmacokinetic analyses confirmed their drug likeness and potential for further development.
The identified inhibitors exhibit strong potential for targeting PARP12 mutants in cancer therapy. Further in vitro and in vivo studies are required to confirm their efficacy and therapeutic viability for clinical applications.
The Associations between Albumin, Globulin, Albumin-to-globulin Ratio, and Frailty in Middle-aged and Older Adults: Evidence from NHANES 2013-2014
Inflammation and nutritional status have significant roles in frailty. While albumin and the albumin-to-globulin ratio (AGR) are recognized as inflammatory and nutritional biomarkers and globulin is associated with inflammation their relationships with frailty remain underexplored. This study explored the relationships between albumin globulin AGR and frailty among middle-aged and older adults utilizing data from the National Health and Nutrition Examination Survey (NHANES) database.
The study was a cross-sectional study with participants aged ≥45 years from the 2013-2014 NHANES database. The frailty assessment was based on a 36-item index of frailty constructed in NHANES excluding nutritional indicators. The relationships between albumin globulin AGR and frailty were analyzed using weighted multivariate regression analyses smooth curve fitting two-segment linear regression models subgroup analyses and interaction tests.
This study involved 1506 middle-aged and older participants with a frailty rate of 42.23%. Nonlinear relationships were identified between albumin AGR and frailty while a linear relationship was observed between globulin and frailty. Two-segment linear regression models demonstrated that the inflection points for albumin and AGR were 3.90 and 1.91 respectively. On the left side of these inflection points albumin and AGR were negatively associated with the prevalence of frailty. On the right side of these inflection points albumin and AGR were not significantly associated with the prevalence of frailty.
This study reveals two threshold effects on frailty in middle-aged and older adults: albumin and AGR. Below specific thresholds both are linked to reduced frailty risk but above these levels neither shows a significant association. Globulin however consistently correlates with increased frailty. These findings highlight nonlinear relationships between albumin AGR and frailty suggesting that maintaining optimal levels of these biomarkers may help prevent frailty.
A Split-Mouth, Randomized, Double-Blind Clinical Trial of a Gelatin Hemostatic Dental Sponge Containing Aloe Vera Nanoparticles for Controlling Bleeding After Mandibular Posterior Teeth Extraction
Hemostatic dental sponges are biodegradable materials and fast hemostats that can help blood clotting in the surgical site and quick repair of the dental surgery site. In this study we investigated the bleeding control (blood absorption ability and active bleeding) of a hemostatic gelatin sponge containing aloe vera nanoparticles as a hemostatic material after the removal of mandibular posterior teeth in a double-blind randomized trial.
A clinical trial was performed on 30 patients (13 males and 17 females) who were referred to the Department of Oral and Maxillofacial Surgery Faculty of Dentistry for extraction of two mandibular molars. The plan was a split-mouth randomized double-blind clinical trial. To investigate the blood absorption ability of a hemostatic sponge containing aloe vera nanoparticles in each patient after tooth extraction the sponge was placed in the socket of the extracted tooth. Sterile gauze was placed on the hemostat sponge containing aloe vera nanoparticles (test group). For the control group the same process was repeated with a sponge without aloe vera nanoparticles. The number of used sterile gauzes was recorded and the mean excess blood weight was measured with a digital scale. Also the amount of bleeding after 1 and 4 hours of tooth extraction was recorded for all patients as an active bleeding time.
The number of sterile gauzes used and the mean excess blood weight used in each group indicate blood absorption. The results showed that there was no significant difference in the amount of sterile gauze between the two groups (P=0.65). In both groups the consumption of three sterile gauzes was the most frequent. However the mean excess blood weight in the control group was significantly higher which indicates the better efficiency of the test group (P=0.04). Besides the examination of the patients showed that in none of the patients of the two groups active bleeding was observed 1 and 4 hours after tooth extraction.
The performance of the test sponge was better than the control sponge in controlling bleeding after tooth extraction. It seems that the obtained results cannot only be related to the presence of aloe vera nanoparticles. The differences in the bleeding control (blood absorption ability and the active bleeding time) for the used sponges can also influence the results. In addition the use of aloe vera in the form of nanoparticles can contribute to early healing effects and other beneficial effects such as antimicrobial effects in the tooth-extracted site.
A Spotlight on PLGA-based Nanoparticles: Pioneering a New Era in the Therapeutics of Cardiovascular Disorders
Cardiovascular disorders (CVDs) are the primary cause of mortality globally and the community is significantly affected when young people suffer from CVDs. Coronary artery disease myocardial infarction fibrosis atherosclerosis pulmonary arterial hypertension thrombosis and ischemic diseases are different types of CVDs which encompass a wide range of conditions that interfere with the functioning of the cardiovascular system. The relevance of nanotechnology in the treatment of CVDs has emerged progressively in previous decades.
This review offers concise insights into the physiochemical characteristics of poly (lactic-co-glycolic acid) (PLGA) imperative for drug delivery. This article highlights the application of PLGA-NPs in myocardial ischemia atherosclerosis myocardial infarction pulmonary artery hypertension valvular heart disease tumour thrombus cardiac myocyte restenosis cardiovascular theranostics vascular disorders and angiogenesis. Further this review gives updates about published patents pertaining to the current state-of-art about PLGA-NPs in CVDs.
An extensive review was undertaken employing the Google Scholar PubMed and ScienceDirect databases using scientific papers published in peer-reviewed journals from 2000 to 2024.
Owing to their minuscule size and increased surface area accessible for surface functionalization the PLGA-NPs offer a cutting-edge technology to provide an efficient platform for controlled and targeted drug delivery therefore imparting tremendous relevance in reducing the occurrence of CVDs.
This has been concluded that PLGA is the highly effective biodegradable copolymer also known as “Smart polymers” because of their biodegradability biocompatibility controlled drug release profile and potential for surface modification with targeting molecules.
Trends in 4D Printed Shape Memory Biomaterials for Tissue Engineering Applications
Shape memory polymers and stimuli-sensitive materials are utilised in 4D printing to develop tissue structures that are dynamic and flexible. The capability of these polymers to react to numerous stimuli like pH light and temperature increases the adaptability and usefulness of tissue engineering applications. The article aims at the application of smart SMPs in 4D printing for tissue engineering emphasising their response to diverse physical and chemical stimuli. The current review article compiled data from previously reported studies by searching in commonly used electronic databases such as Scopus Google Scholar PubMed Science Direct etc. The authors have preferably considered the data from the last 10 years for inclusion. The study addresses developments in smart shape memory polymers and their transformational influence on biological applications. The integrated approach of 4D printing and shape memory biomaterials can potentially improve tissue engineering applications. Researchers can enhance tissue regeneration by utilising the responsive properties of these materials to physiological signals. This allows for the design of dynamic scaffolds that closely imitate the behaviour of real tissue resulting in more efficient tissue regeneration. 4D-printed shape memory biomaterials have the potential to enhance tissue engineering via the use of dynamic and adaptable scaffolds. However some obstacles must be overcome such as material limitations and the capacity to scale up production to achieve successful clinical implementation.
Data-independent Acquisition Mass Spectrometry Reveals Exosomal LAMC1 as a Key Determinant of Lung Adenocarcinoma Radiosensitivity, Independent of EGFR Mutation
This study is formulated to reveal the variables affecting the radio-sensitivity in lung adenocarcinoma (LUAD).
LUAD patients show varied radiotherapy responses. While epidermal growth factor receptor (EGFR) mutations are often used to predict sensitivity their reliability is debated underscoring the need for better biomarkers.
The aim of this study was to identify key functional proteins that regulate the sensitivity of LUAD to radiotherapy and to assess the potential value of exosomal LAMC1 as a clinical predictive marker.
In this study 103 LUAD patients receiving concurrent radiotherapy were included to assess the relationship between EGFR mutation and survival. Intrinsic radio-sensitivity and different radio-sensitivities in 14 LUAD cell lines with/out EGFR mutation were examined based on the surviving fraction at 2 Gy (SF2). Data-independent acquisition (DIA) and Liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomics were used to investigate the proteomics of the LUAD cell lines. Subsequently GO/KEGG enrichment analysis was combined with protein-protein interaction (PPI) network screening for key proteins. Nano-flow cytometry was employed to validate changes in radiosensitivity-associated protein expression within exosomes while siRNA-mediated knockdown was performed to assess the functional impact of specific proteins on LUAD cells.
EGFR mutations were not significantly associated with progression-free survival (PFS)/overall survival (OS). 14 LUAD cell lines displayed intrinsic variations in SF2 and no difference between the EGFR mutation and wild-type groups was reported. 5425 proteins were identified via DIA in 14 LUAD cell lines. After bio-informatics analysis LAMC1 ITGB4 ITGA6 and CD44 were the most representative core differential proteins for the radio-sensitivity in LUAD cells. Notably LAMC1 was confirmed as a radiation-resistant protein. Following radiotherapy LUAD cells secreted exosomes with reduced LAMC1 levels. Moreover LAMC1 knockdown significantly affected cellular proliferation and apoptosis following the irradiation.
LAMC1 serves as a critical functional determinant of radiotherapy resistance in LUAD. Its dynamic changes in exosomes demonstrate potential for predicting radiotherapy response suggesting clinical utility for radiosensitivity assessment and personalized radiotherapy guidance.
Neuroprotective Effect of Naturally Occurring Flavonoids
Flavonoids have a wide range of neuroprotective effects on the brain including the capacity to reduce neuroinflammation shield neurons from harm caused by neurotoxins and maybe improve memory learning and cognitive function. These functions are most likely a result of two similar mechanisms. Inhibiting neurotoxic substance-induced apoptosis and promoting synaptic plasticity and neuronal survival are achieved by first interacting with key protein and lipid kinase signaling pathways in the brain. Second they have positive effects on the vascular system that alter cerebrovascular blood flow and can result in angiogenesis neurogenesis and morphological alterations in neurons. Through these pathways eating foods high in flavonoids has the potential to avoid or delay age-related impairments in cognitive abilities as well as neurodegeneration. Due to the high level of interest in creating new pharmaceuticals that might improve the cognitive function of the brain Flavonoids could be important preparatory substances in the development of a new class of brain-improving drugs.
The Importance of Stem Cells in the Treatment of Neuropathic Pain
Many disorders including heart bone cancer liver and brain disease have been treated using stem cell therapy as a viable alternative. The somatosensory system is affected by a lesion which leads to neuropathic pain (NP) and just a relatively tiny fraction of patients now receive effective care from existing pharmacological medications. There have been studies to show the effectiveness of various stem cells in reducing or treating experimental neurological pain although these studies are uncommon in number. In this review we will summarize the preclinical and clinical research that has been conducted on the effectiveness of several stem cell types such as mesenchymal stem cells bone-derived stem cells and neural stem cells in reducing neurological pain in this study.
Evaluation of Safety and Efficacy of Cuprum metallicum in Zebrafish and Mouse Models as a Potential Drug Candidate for the Management of Seizures
In an alternative medicinal system Cuprum metallicum (CM) is used for the management of seizure-like conditions. However there is a lack of scientific evidence regarding its effect.
The present study aimed to evaluate the effect of CM against Pentylenetetrazole-induced seizures in zebrafish and mice.
Zebrafish were exposed to CM-6C CM-30C and valproic acid for 1 Hr then fish were exposed to pentylenetetrazole to record seizure score and locomotor pattern using ANY maze video tracking software. Mice were pretreated with CM-6C CM-30C and valproic acid for 10 days. After 30 min of the last dose pentylenetetrazole was administered intraperitoneally. Observations during the next 30 min were recorded to detect latency to first myoclonic jerk (FMJ) tonic-clonic seizures and the severity of seizure and survival protection after 24 Hrs.
PTZ exposure significantly decreased the latency from score-1 to score-5 which CM-6C and 30C significantly increased. Furthermore CM-6C and 30C normalized the locomotor activity affected by PTZ exposure. Among the animals treated with the CM-6C and 30C significantly increased latency to FMJ tonic-clonic seizures and survival protection compared to the PTZ group of Cuprum met.
The results of the study indicate that CM 6C and 30C have the potential to work against seizures as they attenuated the PTZ-induced seizures in Zebrafish and BALB/c mice. It could be presumed that CM-6C and 30C could be a beneficial alternative drug candidate for the treatment of epilepsy.
Integrative Analysis of the Impact of Prenatal Depression on the Newborn Intestinal Microbiota
More than 15% of women develop symptoms of depression during pregnancy which often affects the mental and physical development of the newborn by altering its intestinal microbiota. Previous studies revealed that the gut microbiota plays a crucial role in the maturation of systems involved in the gut-brain axis including the gastrointestinal system the immune system and the hypothalamic-pituitary-adrenal system axis.
This study aims to explore the cross-talk between the prenatal depression process and neonatal intestinal microbiota diversity. A total of 100 differentially expressed genes (DEGs) associated with prenatal depression were collected from various scientific publications and databases. Bioinformatics tools were used to analyze these DEGs. The STRING database. ToppGene database and DICE were employed for this integrative analysis.
The network generated by the STRING database identified six pivotal genes: TNF BDNF IL-6 NR3C1 IGF2 and POMC. These genes regulate response to endogenous hormones particularly cortisol secretion in newborns as well as inhibiting serotonin secretion. Moreover these genes are linked to major depressive disorder and other mental diseases contributing to maternal and neonatal gut microbiota dysbiosis. Analysis using ToppGene and DICE’s further validated the biological processes identified by String including the regulation of cellular cortisol secretion metabolic processes and serotonin inhibition.
The bioinformatics tools employed in this study allowed us to identify pivotal genes involved in prenatal depression their associated signaling pathways and their roles in modulating maternal and neonatal gut microbiota.
Formulation, Development and Evaluation of Effervescent Tablet of Green Tea (Camellia sinensis)
Camellia sinensis has an extensive variety of pharmacological properties including neuroprotection photo-aging resistance stress resistance antioxidant anti-tumour hypoglycemic antibacterial and antiviral effects tracing a good potential in addressing illness and preventing disease. Challenges with conventional dosage forms include patient incompatibility improper dosing the inclusion of microplastics etc.
The present work aims to deliver a novel formulation devoid of microplastics and with improved consumer compliance.
Wet granulation was used to formulate 500 mg Camellia sinensis effervescent tablets with improved effervescent time and rapid release. Citric acid and sodium bicarbonate's impacts on disintegration time and pH were examined using a factorial design. Pre-compression variables were assessed for the granule mixture. Post-compression criteria were employed to assess effervescent tablets. The optimum formulation was selected using a central composite response surface and assessment criteria.
The physicochemical characteristics of the developed formulations were significantly influenced by the independent factors. Low concentrations of sodium bicarbonate have positive impact on pH whereas high concentrations of sodium bicarbonate as well as citric acid enhance disintegration time. The design outcomes showed that the optimized effervescent tablets (F10) prepared with 697.5 mg and 448.38 mg of citric acid and sodium bicarbonate respectively had good physicochemical properties.
In compliance with present quality standards factorial design was efficiently utilized for the development of Camellia sinensis effervescent tablets. It was concluded that green tea effervescent tablet (F10) would function as a substitute for conventional green tea powder along with green tea bags as a means of administration.
Thiazolidine-4-one Analogues: Synthesis, In-Silico Molecular Modeling, and In-vivo Estimation for Anticonvulsant Potential
Epilepsy is a critically deep-rooted CNS disorder affecting above 50 million people all over the world. Thus a safe and effective treatment that proves its worth in this ailment is urgently needed. Thiazolidine-4-ones possess the molecules to be used as anticonvulsants. The thiazolidinedione is a cyclic analogue of thiosemicarbazides and thioureas as well as a (bio)isostere of hydantoin (imidazolidine-24-dione) which are recognized as novel anticonvulsant designs.
This study aimed to develop and evaluate a novel thiazolidine-4-one derivative by three-component condensation in one pot reaction method.
A novel thiazolidine-4-one derivative was formulated by three-component condensation. The selected OH (Alcohol) derivatives were found to be more potent; hence a molecular docking study against a selected target LGI1 LRR domain was performed. Various analytical tests like FTIR and H1 NMR were accomplished. The FTIR was used to validate the existence of multiple functional moieties like C-S O-H C=O C-N N=O C-NH C-O in the wave region from 3075 cm-1 – 1236 cm-1 and H1 NMR was employed to ascertain if the synthesized analogues had the complete set of protons. Then the anti-seizure activity of the selected compound was examined using PTZ models in mice at three successive doses i.e. 25 50 and 100mg/kg and compared with standard ethosuximide.
The docking simulations were initiated using PyMOL after the binding site was determined and the receptor and ligand were suitably prepared. It showed higher binding frequency in comparison to the standard marketed drug Ethosuximide. FTIR and H1 NMR spectroscopy were used to characterize the chemical components. Numerous functional groups including O-H (alcohol) C=O (ketones) N=O C-NH C-N C-S and C-O bending stretching were visible in the synthesized molecule accordingly. The synthesized compound was effective in inhibiting the convulsions at the concentration of 100 mg/kg.
The novel thiazolidine-4-one derivative showed promising activity and could be considered for further investigation and dosage form preparation.
Antidepressant Potential of Hispidulin Present in S. barbata D. Don: Mechanistic Insights through Neurochemical and Behavioral Assessments
This study aims to investigate the antidepressant properties of Hispidulin a flavonoid present in Scutellaria barbata D. Don. The selection of Hispidulin stems from its notable inhibitory activity against Xanthine Oxidase (XO) a parameter in the pathophysiology of depression.
Mice were subjected to a rigorous evaluation using a murine model of Chronic Unpredictable Mild Stress (CUMS) to induce depression for 21 days and antidepressant properties were rigorously assessed using the Tail Suspension Test (TST) Forced Swim Test (FST) and Open Field Test (OFT). Imipramine and fluoxetine were used as standard drugs. Additionally neurochemical analyses were conducted to quantify serotonin (5-HT) norepinephrine (NE) and dopamine (DA) levels in the cortex hippocampus and hypothalamus. Further mechanistic insights were sought through the estimation of monoamine oxidase (MAO) activity and assessment of antioxidant enzyme levels in the brain. Plasma nitrite and corticosterone levels were also measured to delineate the underlying mechanism of action.
Hispidulin demonstrated significant antidepressant effects as evidenced by reduced immobility time in TST and FST and increased exploratory behavior in OFT. Neurochemical analysis revealed restoration of 5-HT NE and DA levels in key brain regions. Furthermore Hispidulin modulated MAO activity and enhanced antioxidant enzyme levels in the brain. Plasma nitrite levels were elevated indicating enhanced nitric oxide synthesis while corticosterone levels were reduced.
Our findings indicate that Hispidulin exerts potent antidepressant effects potentially mediated through its influence on monoaminergic neurotransmitters MAO activity and antioxidant defenses. These results provide valuable mechanistic insights into the antidepressant action of Hispidulin supporting its potential therapeutic application in depressive disorders.
Identification of Phytoconstituents from Natural Product Database as SIRT2 Inhibitors for Potential Role in Alzheimer’s Disease: An In-Silico Screening
We aimed to conduct in silico screening of the potential phytoconstituent from a natural product database to find SIRT2 inhibitors.
Alzheimer's disease (AD) is the most prevalent type of dementia characterized by behavioral and mental symptoms as well as a progressive loss of cognitive ability. Since SIRT2 may be detrimental to neurological illnesses it is a prime target for research into SIRT2 inhibitors.
To identify the SIRT2 inhibitors and their role in AD.
We have utilized NPAtlas database and screened using pharmacophore-based virtual screening molecular docking and simulation. The Natural Products Atlas provides unrestricted access to various natural products derived from bacteria and fungi allowing researchers to investigate and visualize the extensive chemical diversity in the natural world.
From in silico screening data we have found phytoconstituents that could function as SIRT2 inhibitors. Six phytoconstituents were identified using pharmacophore-based virtual screening. According to molecular docking Kurasoin B outperformed the reference molecule regarding binding energy. Kurasoin B exhibited a binding affinity of -12.543 kcal/mol whereas the binding affinity of the reference molecule was -12.089 kcal/mol. The Kurasoin B complex with SIRT2 was determined to be stable throughout the simulation by performing MD simulation with an RMSD of 2.88 (Å) whereas the reference and free protein displayed RMSDs of 3.74 and 4.70 (Å) respectively.
In silico studies and data analysis suggest that Kurasoin B may be able to suppress the SIRT2 protein for managing AD.
ACKNOWLEDGEMENT TO REVIEWERS
Mechanism of Shashen Maidong Decoction in the Treatment of Radiation Pneumonitis Based on Network Pharmacology and Molecular Docking
Radiation therapy is a crucial method used to treat various tumors but it can lead to radiation pneumonitis. Shashen Maidong Decoction (SMD) is clinically used to treat radiation pneumonitis but the exact mechanism remains unclear.
Herbal components and targets of SMD were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) the Encyclopedia of Traditional Chinese Medicine (ETCM) and Swiss Target Prediction platforms. Moreover disease-related targets were retrieved from the GeneCards database. A Protein-protein Interaction (PPI) network was constructed using the STRING database and analyzed using the Cytoscape software. In addition Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using the DAVID database. Subsequently the disease-active component-target network and drug-pathway-target network were constructed using Cytoscape. The molecular docking results were validated and visualized using Auto Dock and PyMOL software.
In this study 115 conserved active ingredients 316 drug targets and 355 radiation pneumonitis targets were identified. Among these 75 targets were identified as intersecting targets. GO enrichment analysis revealed 494 biological processes 36 cell components and 59 molecular functions. KEGG analysis uncovered 118 signaling pathways including the IL17 signaling pathway TNF signaling pathway HIF-1 signaling pathway etc. The molecular docking results showed the core active ingredients of SMD including quercetin kaempferol beta-carotene and naringenin to have strong binding ability with the core targets.
This study preliminarily confirmed that SMD may act on the TNF IL17 and HIF-1 signaling pathways to exert its therapeutic effects on radiation pneumonitis by regulating the expression of inflammatory factors.
Production, Characterization, and Molecular Dynamic Study of Antidiabetic and Antioxidative Peptides of Fermented Cheese Whey with Anti-inflammatory Properties using Limosilactobacillus fermentum
This study aims to valorise cheese whey waste by converting it into bioactive peptides that have several health benefits potentially leading to the development of nutraceuticals and functional foods and also used in the pharmaceutical industry.
The study evaluates the antidiabetic antioxidative and anti-inflammatory properties of fermented cheese whey with Limosilactobacillus fermentum (M4) along with the production of antioxidative and antidiabetic peptides. SDS-PAGE and 2D-PAGE were also performed to identify proteins by molecular weight and isoelectric point while RP-HPLC distinguished peptide fractions. Peptide sequences from 2D gel spots were identified using RPLC/MS and RP-HPLC analyzed 3 kDa and 10 kDa permeates. Peakview software characterized the LC/MS results and FTIR analysis measured structural changes in bioactive peptides.
The antioxidative and antidiabetic properties in cheese whey fermented with M4 showed a progressive growth over extended incubation periods higher effects were observed after fermentation for 48 hours. Inhibitory activities in α-glucosidase α-amylase & lipase were found to be 65.39% 66.09% and 56.74% respectively. ABTS assay was performed to measure antioxidant activity (63.39%) and the highest proteolytic activity (7.62 mg/ml) was measured at 2.5% inoculation rate for 48 hours. In SDS-PAGE protein bands between 10 & 30 kDa were observed whereas peptide spots within the range of 10 to 70 kDa were also visualized on the 2D-PAGE. RP-HPLC was used to distinguish different fractions of a peptide. Peptide sequences from 2D gel spots were identified using RP-HPLC & RPLC/MS. Peakview software was utilized to characterize the LC/MS results. Sequences of peptides generated from α-lactalbumin and β-lactoglobulin were searched in the BIOPEP database to validate the antidiabetic and antioxidative activities of fermented cheese whey peptides. LPS-fermented cheese whey at a concentration of 0.50 mg/mL significantly suppressed the production of pro-inflammatory cytokines as well as the mediators that govern them including IL-6 IL-1β NO and TNF-α in RAW 264.7 cells. FTIR was used in the analysis of protein secondary structure and conformational changes.
This study aims to produce antidiabetic and antioxidative peptides from dairy waste and cheese whey.
Astragalus Injection Modulates the Pharmacokinetics of Doxorubicin and CYP450 Enzymes
Doxorubicin (DOX) is a widely used anthracycline antibiotic for the treatment of breast cancer liver cancer lymphoma and other malignant tumors. However its clinical application is limited by the side effects and drug resistance. Astragalus injection has been combined with DOX in the treatment of cancer which improves the curative effect and reduces drug resistance. This study investigated the interaction between DOX and Astragalus injection and elucidated the potential mechanism.
The pharmacokinetics of DOX injection (7 mg/kg intraperitoneal injection) with or without Astragalus injection (4.25 mL/kg/day for 14 days intraperitoneal injection) were investigated in plasma from male Sprague-Dawley rats (n = 6) by UPLC-MS/MS. The group without the Astragalus injection was set as the control group. Additionally the effects of Astragalus injection on CYP450 enzyme activities were assessed using a rat liver microsome incubation system with cocktail probe drugs.
Astragalus injection significantly increased the Cmax (2090.01 ± 99.60 vs. 5262.77 ± 111.15 ng/mL) and AUC0-t (1190.23 ± 104.43 vs. 3777.27 ± 130.55 μg/L × h) and prolonged the t1/2α (0.09 ± 0.02 vs. 0.14 ± 0.04 h) of DOX. Astragalus injection significantly inhibited the activity of CYP1A2 CYP2C9 CYP2E1 and CYP3A4 and enhanced the activity of CYP2D1 with a metabolic elimination rate of 30.11 ± 2.67% vs. 19.66 ± 3.41% 35.95 ± 2.57% vs. 23.26 ± 3.57% 13.43 ± 2.56% vs. 9.06 ± 2.51% 47.90 ± 6.30% vs. 25.87 ± 2.55% 17.62 ± 1.49% vs. 24.12 ± 2.91% respectively (p < 0.05).
The co-administration of DOX and Astragalus injection alters the systemic exposure of DOX by affecting the metabolism of DOX and the activity of CYP450 enzymes. These findings highlight the importance of drug-drug interactions when combining Astragalus injection with DOX and provide a basis for optimizing combination therapies to address DOX resistance and toxicity.
Medicinal Plants in the Treatment of Tuberculosis: A Systematic Review
Tuberculosis (TB) is the most common disease that affects the lungs and it is associated with Mycobacterium tuberculosis infection. Many synthetic medications such as pyrazinamide isoniazid and ethambutol are available to treat TB; however their adverse effects are severe. Medicinal herbs have lately become popular safe and effective alternative treatments for TB.
The purpose of this systematic review was to assess the possible use of natural plants in the development of herbal treatments and remedies for TB by studying the medicinal plants and phytochemicals that have been used for the disease. Information was gathered from a variety of sources including Bentham Elsevier Springer Nature Google Scholar PubMed Sci-Finder and the Web of Science. For the investigation common and scientific names of plants as well as terms like “mycobacterium tuberculosis” “herbal plants” “flavonoids” and “alkaloids” were employed. In the end 376 plants belonging to 83 families were discovered and details about each plant family as well as the section of the plant utilized chemical components extract and strain were extracted.
The findings showed that although flavonoids and alkaloids were the most prevalent naturally occurring substances found in plants the Fabiaceae family had a greater potential to eradicate TB.
The leaf portion was shown to be more active and the S-37 RV strain of Mycobacterium TB was employed more frequently.