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Traditional medicinal plants have attracted scientific interest due to their bioactive compounds, and the levels of their constituents vary with location and altitude. The present study was designed to evaluate the pharmacological potential of two selected traditional medicinal plants, Mikania micrantha and Ageratum houstonianum collected from two sites, Murlen National Park (MNP) and Dampa Tiger Reserve (DTR), located at different altitudes. Both plant species are used by local traditional healers in Mizoram, Northeast India, to treat various health problems. We hypothesized that altitudinal variation would affect these plants' chemical composition and bioactive potential. Plant extracts were evaluated for antioxidant and cytotoxic activities. The results show that the plants located at a higher altitude, i.e., MNP, showed higher TPC (615.7 ± 0.58 and 453.80 ± 0.95 µg gallic acid equivalents/mg of plant extract dry weight (µg GAE/mg) for M. micrantha and A. houstonianum , respectively) and TFC (135.4 ± 0.46 and 120.66 ± 1.93 µg quercetin equivalents/mg of plant extract dry weight (µg GE/mg) for M. micrantha and A. houstonianum, respectively). The extract of A. houstonianum. (MNP) exhibited significantly greater antioxidant activity against ABTS radicals (IC50 241.6 µg/mL) as compared to the extract of A. houstonianum (DTR) (IC50 371.2 µg/mL). The composition of the bioactive compounds present in the plants was determined using UPLC-ESI MS/MS and GC/MS, which detected five and ten compounds in the A. houstonianum and M. micrantha extracts, respectively. Plant species collected from the Murlen National Park site had high bioactivity potential and contained several bioactive compounds. A distinct variation between the volatile and non-volatile compounds was revealed. The collective data in this study show the influence of altitude on the biological compound production of selected medicinal plants. The findings will be utilized in the plant material needed for developing bioactive formulations.
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The advancement in nanotechnology has completely revolutionized various fields, including pharmaceutical sciences, and streamlined the potential therapeutic of many diseases that endanger human life. The synthesis of green nanoparticles by biological processes is an aspect of the newly emerging scientific field known as "green nanotechnology". Due to their safe, eco-friendly, nontoxic nature, green synthesis tools are better suited to produce nanoparticles between 1 and 100 nm. Nanoformulation of different types of nanoparticles has been made possible by using green production techniques and commercially feasible novel precursors, such as seed extracts, algae, and fungi, that act as potent reducing, capping, and stabilizing agents. In addition to this, the biofunctionalization of nanoparticles has also broadened its horizon in the field of environmental remediation and various novel therapeutic innovations including wound healing, antimicrobial, anticancer, and nano biosensing. However, the major challenge pertaining to green nanotechnology is the agglomeration of nanoparticles that may alter the surface topology, which can affect biological physiology, thereby contributing to system toxicity. Therefore, a thorough grasp of nanoparticle toxicity and biocompatibility is required to harness the applications of nanotechnology in therapeutics.
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Restauración y Remediación Ambiental , Tecnología Química Verde , Nanopartículas , Nanopartículas/química , Tecnología Química Verde/métodos , Restauración y Remediación Ambiental/métodos , Humanos , Nanotecnología/métodosRESUMEN
Most cells in solid tumors are exposed to oxygen levels between 0.5% and 5%. We developed an approach that allows collection, processing, and evaluation of cancer and non-cancer cells under physioxia, while preventing exposure to ambient air. This aided comparison of baseline and drug-induced changes in signaling pathways under physioxia and ambient oxygen. Using tumor cells from transgenic models of breast cancer and cells from breast tissues of clinically breast cancer-free women, we demonstrate oxygen-dependent differences in cell preference for epidermal growth factor receptor (EGFR) or platelet-derived growth factor receptor beta (PDGFRß) signaling. Physioxia caused PDGFRß-mediated activation of AKT and extracellular regulated kinase (ERK) that reduced sensitivity to EGFR and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) inhibition and maintained PDGFRß+ epithelial-mesenchymal hybrid cells with potential cancer stem cell (CSC) properties. Cells in ambient air displayed differential EGFR activation and were more sensitive to targeted therapies. Our data emphasize the importance of oxygen considerations in preclinical cancer research to identify effective drug targets and develop combination therapy regimens.
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BACKGROUND AND OBJECTIVES: The role of various genetic markers including alpha synuclein, Parkin, etc., is known in the pathogenesis of Parkinson's disease (PD). Novel genetic markers including paraoxonase 1 (PON1) have also been linked to PD pathogenesis in recent studies. The PON1 L55M allele carriers may have defective clearance of environmental toxins and may result in increased susceptibility to PD. Hence, we studied the role of PON1 L55M polymorphism in PD among a North Indian population. MATERIALS AND METHOD: Seventy-four PD patients and 74 age- and sex-matched controls were recruited in this hospital-based case-control study. Baseline characteristics were recorded using structured questionnaire. DNA was extracted from 3-4 ml of venous blood, followed by PCR and restriction digestion. PON1 L55M genotypes were visualized as bands: LL (177 bp), LM (177, 140 bp) and MM (140,44 bp) on 3% agarose gel. Mann-Whitney U test and Chi-squared test were used for comparing two groups of skewed and categorical variables, respectively. Measures of strength of association were calculated by binary regression analysis. P value < 0.05 was considered as significant. RESULTS: Parkinson's disease patients had significantly higher exposure to pesticides (12.2%; P (organophosphate exposure) < 0.001) and well water drinking (28.4%; P = 0.006) compared to controls. Frequency distribution of LL, LM, MM genotypes was 67.5% (50/74), 28.4% (21/74), and 4.1% (3/74), respectively, for cases and 72.6% (54/74), 26% (19/74) and 1.4% (1/74), respectively, for controls. PON1 L55M genotype distribution between Parkinson's disease cases and controls was not significant (P = 0.53). PON1 L55M polymorphism was not associated with PD after adjusting for confounders by binary regression analysis. CONCLUSION: There was no significant association between PON1 L55M polymorphism and PD. Larger population-based studies would be required from India before drawing any definite conclusions.
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Arildialquilfosfatasa , Predisposición Genética a la Enfermedad , Enfermedad de Parkinson , Humanos , Arildialquilfosfatasa/genética , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/epidemiología , India/epidemiología , Femenino , Masculino , Estudios de Casos y Controles , Persona de Mediana Edad , Predisposición Genética a la Enfermedad/genética , Anciano , Polimorfismo Genético/genética , GenotipoRESUMEN
The objective of this prospective observational study was to assess the growth and body composition of term small-for-gestational-age (SGA) infants from birth to 6 months and evaluate the effect of catch-up growth (CUG) on body composition. Term SGA newborns were recruited at birth. Anthropometry and body composition were evaluated at 3 days, 6, 10 and 14 weeks, and 6 months. Fat and fat-free mass (FM and FFM) were compared between infants with and without CUG (increase in weight Z-score by > 0·67) by air displacement plethysmography. Factors that could affect body composition and CUG, including parents' BMI and stature, infants' birth weight, sex and feeding, were evaluated. A total of 143 SGA newborns (sixty-six boys) with birth weight of 2336 (sd 214) g were enrolled; 109 were followed up till 6 months. Median weight Z-score increased from -2·3 at birth to -1·3 at 6 months, with 51·9 % of infants showing CUG. Infants with CUG had higher FM (1796 (sd 491) g v. 1196 (sd 474) g, P < 0·001) but similar FFM (4969 (sd 508) g v. 4870 (sd 622) g, P = 0·380), and consequently higher FM percentage (FM%) (26·5 (sd 5·8) v. 19·7 (sd 6·9), P < 0·001), compared with those without CUG. Lower birth weight, exclusive breast-feeding and higher parental stature were positively associated with CUG. In conclusion, CUG in term SGA infants in the first 6 months of life was almost entirely attributable to greater gain in FM. Follow-up of this cohort will provide insight into the long-term effect of disproportionate gain in FM in early infancy in SGA babies.
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Cancer-induced skeletal muscle defects differ in severity between individuals with the same cancer type. Cancer subtype-specific genomic aberrations are suggested to mediate these differences, but experimental validation studies are very limited. We utilized three different breast cancer patient-derived xenograft (PDX) models to correlate cancer subtype with skeletal muscle defects. PDXs were derived from brain metastasis of triple-negative breast cancer (TNBC), estrogen receptor-positive/progesterone receptor-positive (ER+/PR+) primary breast cancer from a BRCA2-mutation carrier, and pleural effusion from an ER+/PR- breast cancer. While impaired skeletal muscle function as measured through rotarod performance and reduced levels of circulating and/or skeletal muscle miR-486 were common across all three PDXs, only TNBC-derived PDX activated phospho-p38 in skeletal muscle. To further extend these results, we generated transformed variants of human primary breast epithelial cells from healthy donors using HRASG12V or PIK3CAH1047R mutant oncogenes. Mutations in RAS oncogene or its modulators are found in approximately 37% of metastatic breast cancers, which is often associated with skeletal muscle defects. Although cells transformed with both oncogenes generated adenocarcinomas in NSG mice, only HRASG12V-derived tumors caused skeletal muscle defects affecting rotarod performance, skeletal muscle contraction force, and miR-486, Pax7, pAKT, and p53 levels in skeletal muscle. Circulating levels of the chemokine CXCL1 were elevated only in animals with tumors containing HRASG12V mutation. Because RAS pathway aberrations are found in 19% of cancers, evaluating skeletal muscle defects in the context of genomic aberrations in cancers, particularly RAS pathway mutations, may accelerate development of therapeutic modalities to overcome cancer-induced systemic effects. SIGNIFICANCE: Mutant RAS- and PIK3CA-driven breast cancers distinctly affect the function of skeletal muscle. Therefore, research and therapeutic targeting of cancer-induced systemic effects need to take aberrant cancer genome into consideration.
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Músculo Esquelético , Humanos , Femenino , Animales , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Ratones , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Mutación , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/metabolismoRESUMEN
This study aims to develop pH-sensitive and controlled release of ciprofloxacin from ciprofloxacin-loaded grafted chitosan-coated zinc oxide nanoparticles (Cip@Gchit/Zn-NPs) for the treatment of bacterial infections in the human colon. For this aim, first, the chitosan-g-poly(itaconic acid) [Chit-g-poly (Itac)] was synthesized via grafting of itaconic acid onto chitosan in the presence of cerium ammonium nitrate (CAN) under an inert atmosphere using conventional methods, while zinc oxide nanoparticles (Zn-NPs) were prepared via sol-gel technique. Characterization of the synthesized Cip@Gchit/Zn-NPs was analyzed using XRD, FT-IR, SEM, TGA, and zeta potential analysis. The antibacterial efficacy of Cip@Gchit/Zn-NPs against three pathogenic bacteria, namely Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus, was superior to that of tetracycline reference drugs, as evidenced by larger inhibition zones. Cytotoxicity assessment of Cip@Gchit/Zn-NPs on the human chondrocyte cell line C28/I2 via MTT assay revealed 100 % cell viability at a concentration of 500 µg/mL. The loading efficiency of ciprofloxacin into Gchit/Zn-NPs was evaluated at various ratios, demonstrating lower loading efficiency; however, sustained release of ciprofloxacin from Cip@Gchit/Zn-NPs was excellent, with 98.13 % release observed at pH 7.2 over 10 h. Kinetic analysis of ciprofloxacin release followed the first-order kinetic models.
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Antibacterianos , Quitosano , Ciprofloxacina , Portadores de Fármacos , Succinatos , Quitosano/química , Ciprofloxacina/farmacología , Ciprofloxacina/química , Ciprofloxacina/administración & dosificación , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Concentración de Iones de Hidrógeno , Portadores de Fármacos/química , Succinatos/química , Humanos , Nanopartículas/química , Liberación de Fármacos , Pruebas de Sensibilidad Microbiana , Staphylococcus aureus/efectos de los fármacos , Óxido de Zinc/química , Óxido de Zinc/farmacología , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
This review explores the realm of structural modifications and broad spectrum of their potential applications, with a special focus on the synthesis of xanthan gum derivatives through graft copolymerization methods. It delves into the creation of these derivatives by attaching functional groups (-OH and -COOH) to xanthan gum, utilizing a variety of initiators for grafting, and examining their diverse applications, especially in the areas of food packaging, pharmaceuticals, wastewater treatment, and antimicrobial activities. Xanthan gum is a biocompatible, biodegradable, less toxic, bioactive, and cost-effective natural polymer derived from Xanthomonas species. The native properties of xanthan gum can be improved by cross-linking, grafting, curing, blending, and various modification techniques. Grafted xanthan gum has excellent biodegradability, metal binding, dye adsorption, immunological properties, and wound healing ability. Owing to its remarkable properties, such as biocompatibility and its ability to form gels resembling the extracellular matrix of tissues, modified xanthan gum finds extensive utility across biomedicine, engineering, and the food industry. Furthermore, the review also covers various modified derivatives of xanthan gum that exhibit excellent biodegradability, metal binding, dye adsorption, immunological properties, and wound healing abilities. These applications could serve as important resources for a wide range of industries in future product development.
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Polímeros , Polisacáridos Bacterianos , Polisacáridos Bacterianos/química , GelesRESUMEN
OBJECTIVES: Patient involvement in mental health professional education is required by policy but lacks a robust evidence base. The impact of involvement in education on patients with mental health conditions may differ from that of patients with other conditions. This study aims to review the impact of involvement in mental health professional education on the patients with mental health conditions involved. SETTING: Electronic databases MEDLINE, PubMed, AMED, EMBASE, PsycINFO, Emcare, BNI, HMIC and CINAHL were systematically searched to find articles reporting on health professional teaching interventions involving patients with mental health conditions and the psychological, social or physical impact of involvement. The search took place in August 2023. RESULTS: Findings from 20 articles were amalgamated into four synthesised findings: (1) Impact of general involvement (2) impact of making a difference through teaching, (3) impact of new relationships and (4) impact of talking about experiences. CONCLUSIONS: Patient involvement in mental health professional education can be beneficial for patients with mental health conditions when their experiences are respected and valued as expertise by students and academic staff. The experiences of patient educators in the mental health field are unique in that teaching activities interact with their mental health. Future research should evaluate patient involvement in the mental health field separately and report research findings according to reporting guidelines. PROSPERO REGISTRATION NUMBER: CRD42020224907.
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Participación del Paciente , Humanos , Investigación Cualitativa , Personal de Salud/educación , Personal de Salud/psicología , Trastornos Mentales/terapia , Salud Mental , Servicios de Salud MentalRESUMEN
A total of 32 Landlly crossbred sows were categorized into three groups based on their body condition score (BCS) on the 90th day of gestation viz. low, moderate, and high body condition groups. BCS assessments were subsequently conducted on the 102nd day, at farrowing, and on the 7th, 17th, 27th, and 42nd day postpartum, along with measurements of ultrasonic backfat thickness and body weight. Key reproductive performance traits, including total number born (TNB) and alive (TLA), stillbirths, mummification, and litter weight at birth and weaning, were recorded. Several physiological, health, biochemical, and hematological parameters were also estimated at different lactation stages. Analysis of the data revealed that TNB, TLA (P<0.04), and weaned piglets (P<0.01), as well as litter weight at birth (P<0.08) and weaning (P<0.08), were significantly higher in the low BCS group. Meanwhile, the weaning to estrous interval (P<0.04) was optimized in the high and moderate BCS groups. However, sows with high body condition exhibited higher stillbirths and pre-weaning mortality. Additionally, the order of increasing body condition correlated with superior colostrum quality, characterized by higher IgG levels (P<0.02), and increased average milk yield during early and mid-lactation (P<0.03). A high occurrence of postpartum dysgalactia syndrome (PDS) was evident in obese sows (P<0.001). Moreover, a positive correlation was found between the body condition of sows at late gestation and cortisol concentration throughout lactation across the three BCS groups (P<0.0001). Furthermore, a strong positive correlation was observed between the postpartum serum concentration of T3 (thyroid hormone) (P<0.002) and the prepartum body condition of sows. Based on these findings, maintaining sows with a moderate body condition (BCS of 3) and a backfat thickness of 21 mm in the breeding herd is recommended for enhancing profitability and productivity at the farm level.
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Mortinato , Enfermedades de los Porcinos , Embarazo , Porcinos , Animales , Femenino , Peso al Nacer , Mortinato/veterinaria , Dieta/veterinaria , Reproducción , Lactancia , Destete , Tamaño de la CamadaRESUMEN
The biologic basis of genetic ancestry-dependent variability in disease incidence and outcome is just beginning to be explored. We recently reported enrichment of a population of ZEB1-expressing cells located adjacent to ductal epithelial cells in normal breasts of women of African ancestry compared to those of European ancestry. In this study, we demonstrate that these cells have properties of fibroadipogenic/mesenchymal stromal cells that express PROCR and PDGFRα and transdifferentiate into adipogenic and osteogenic lineages. PROCR + /ZEB1 + /PDGFRα+ (PZP) cells are enriched in normal breast tissues of women of African compared to European ancestry. PZP: epithelial cell communication results in luminal epithelial cells acquiring basal cell characteristics and IL-6-dependent increase in STAT3 phosphorylation. Furthermore, level of phospho-STAT3 is higher in normal and cancerous breast tissues of women of African ancestry. PZP cells transformed with HRasG12V ± SV40-T/t antigens generate metaplastic carcinoma suggesting that these cells are one of the cells-of-origin of metaplastic breast cancers.
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Neoplasias de la Mama , Humanos , Femenino , Incidencia , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/genética , Receptor de Proteína C Endotelial , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas , Células EpitelialesRESUMEN
Bone Morphogenetic Proteins play a significant role in ovarian physiology and contribute to the reproductive fitness of mammals. The BMPR-1B/FecB mutation, a loss of function mutation increases litter size by 1-2 with each number of mutated alleles in sheep. Considering demand-supply gap of the meat industry, and low replacement rate of indigenous caprine species, the conservative BMPR-1B locus can be explored, and FecB mutated goats can be produced. The experiment one produced CRISPR/Cas mediated KO transferable caprine embryos, and experiment two generated caprine embryos with desired FecB mutation using Easi-CRISPR strategy. In the KO experiment, Cas9 and BMPR-1B guide RNA (100:100ng/ul) were electroporated into single stage caprine zygotes at 750V, 10 ms and 1pulse using Neon transfection system. In the second experiment, phosphorothioate (PS) modified single-stranded oligodeoxynucleotide (ssODN) was used as an HDR template along with CRISPR components (100:100ng/ul, ssODN 100ng/ul). The precise time and method of electroporation, RNP format of CRISPR components and PS modified asymmetric ssODN were the factors that affected the production of mosaicism free BMPR-1B edited caprine embryos. The editing efficiency of KO and KI experiments was 68.52 and 63.16% respectively, and successful production of goats with higher mean ovulation rate can be realized with addition of embryo transfer technology to these experiments.
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Sistemas CRISPR-Cas , Cabras , Femenino , Animales , Ovinos , Cabras/genética , Mutación , Alelos , Terapia de Electroporación/veterinariaRESUMEN
Introduction The medial and lateral menisci of the knee joint are the functional unit that helps to increase the depth of articular surfaces on the head of a tibia for the reception of femoral condyles. Menisci are important for the distribution of load and thus help to reduce stress on the knee joint. The anatomical knowledge of morphology and morphometry of menisci is vital while performing surgeries in cases of meniscal injury. The study aimed to define the variational anatomy of the menisci of the knee joint. Material and Methods Ninety-six cadaveric knees of 48 cadavers were included in the study. Different shapes of both; lateral and medial menisci were recorded. The peripheral lengths and inner lengths of the menisci were measured with the nonelastic cotton thread. Menisci were divided into three parts; anterior, middle, and posterior. The maximum width and thickness of each part of the menisci were measured and documented. Distance between the medial and lateral meniscus in each knee was measured at the anterior and posterior ends. The most anterior and the most posterior part of each meniscus was determined and the distance between these parts of each meniscus was measured and recorded as the distance between two horns. Results Four morphological types of menisci were found; in medial menisci, the most common was crescentshaped (53%), and in lateral menisci, the most common shape was cshape (62.5%). The average peripheral length of the medial menisci was 92.0 mm and the lateral menisci was 96.08 mm while the average inner length of the medial and lateral meniscus was 56.19 mm and 58.92 mm respectively. The anterior third of the medial as well as lateral meniscus was thinnest while the posterior third was thickest. The width of the medial menisci was less at the anterior end and was more at the posterior ends while the width of the lateral meniscus was almost the same at the anterior, middle, and posterior ends. Conclusion The findings of the present study will be helpful for surgeons while planning and performing surgical procedures and for anatomists during routine teaching.
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Introduction Due to the variable degree of pneumatization, the shape and size of the sphenoid sinus are irregular. An endoscopic intranasal transsphenoidal approach is made in sphenoid sinus pathologies, sphenoid sinusitis, and sellar and parasellar diseases. A diagnostic approach to the sphenoid sinus is also done to get a better MRI scan of the pituitary. The present study aims to describe the variant types of sphenoid sinus, morphometry, anatomy, and relations of sphenoid sinus, which will be helpful to surgeons during an endoscopic approach to the sphenoid sinus. Materials and methods We studied 76 cadaveric sphenoid sinuses that were exposed by taking a sagittal section of 38 formalin-fixed cadaveric heads. After examining the inter-sphenoidal septum, it was removed to observe the inside aspect of the sphenoid sinus. Different dimensions of the sinus were noted down. The bulges inside the sinus due to neurovascular structures in relation to the sinus were observed. Results The most prominent type found was the sellar in 68.4% of cases preceded by the postsellar in 23.7% of cases. Presellar type of pneumatization was seen only in 7.9% of cases and the conchal type was absent. Intersphenoid septum was seen in 92,1% of cases, out of which 11.4% of septums were deficient on the posterior aspect. An internal carotid artery bulge in the sphenoid sinus was seen in 46% of cases. In 27.6% and 19.7% of sphenoid sinuses, bulging of the optic and vidian nerves, respectively, were seen. Some of these structures were dehiscent in the sphenoid sinus. Conclusions To get more space in the sphenoid sinus, the septa in the sinus are removed by surgeons, which may damage the walls of the sphenoid sinus. Knowledge of the relations of neurovascular structures with the sphenoid sinus will be helpful to surgeons during the transsphenoidal endoscopic approach to avoid any injury to these structures.
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The median nerve is one of the important nerves of the upper limb which supplies the muscles of the front of the forearm, muscles of the hand, and skin of the hand. Many works of literature mentioned its formation by the fusion of two roots, the medial root from the medial cord and the lateral root from the lateral cord. But multiple variations in the median nerve formation have clinical importance from surgical and anesthetic points of view. For the study purpose, we dissected 68 axillae of 34 formalin-fixed cadavers. Out of 68 axillae, two (2.9%) showed median nerve formation by a single root, 19 (27.9%) showed median nerve formation by three roots, and three (4.4%) showed median nerve formation by four roots. A normal pattern of median nerve formation by fusion of two roots was seen in 44 (64.7%) axilla. The knowledge of variant patterns of median nerve formation will be helpful to surgeons and anesthetists while performing surgical or anesthetic procedures in the axilla to avoid any injury to the median nerve.
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[This retracts the article DOI: 10.1007/s12070-020-01849-2.].
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Introduction: Diabetes mellitus (DM) is a metabolic disorder that results in glucose accumulation in the blood, accompanied by the production of advanced glycation end products (AGEs) through glycation of cellular proteins. These AGEs interfere with insulin signaling and prevent GLUT4 membrane translocation, thereby promoting the accumulation of more glucose in the blood and causing post-diabetic complications. Methods: In this study, we examine the anti-diabetic potential of Lyonia ovalifolia (Wall.) Drude, a well-known ethnomedicinal plant of the Indian Himalayas. Considering its various medicinal properties, we analyzed its ethanolic extract and various solvent fractions for in vitro antiglycation activity and antidiabetic potential, i.e., stimulation of GLUT4 translocation. Result and Discussions: The results showed that the extract and fractions exhibited increased antiglycation activity and an increased level of GLUT4 translocation. Analysis of a further 12 bioactive compounds of ethanolic extract, identified through LC-ESI-QTOF-MS/MS, revealed the presence of three new compounds: leucothol B, rhodoterpenoids A, and leucothol A. Moreover, we performed molecular docking of identified compounds against key proteins of diabetes mellitus: the sirtuin family of NAD (+)-dependent protein deacetylases 6 (SIRT6), aldose reductase (AR), and tyrosine kinase (TK). The results showed that flavonoid luteolin showed the best binding affinity ((-12.3 kcal/mol), followed by eriodictyol, astilbin, and syringaresinol. An ADMET study showed that luteolin, eriodictyol, astilbin, and syringaresinol may be promising drug candidates belonging to the flavonoid class of compounds, with no harmful effects and complying with all the drug-likeness guidelines. Furthermore, molecular dynamics (MD) simulations on a 50 ns timescale revealed that AR protein was most stable with luteolin throughout the simulation period. Therefore, this study reveals for the first time that L. ovalifolia plays an important role in insulin homeostasis, as shown in in vitro and in silico studies.
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Skeletal muscle dysfunction or reprogramming due to the effects of the cancer secretome is observed in multiple malignancies. Although mouse models are routinely used to study skeletal muscle defects in cancer, because of species specificity of certain cytokines/chemokines in the secretome, a human model system is required. Here, we establish simplified multiple skeletal muscle stem cell lines (hMuSCs), which can be differentiated into myotubes. Using single nuclei ATAC-seq (snATAC-seq) and RNA-seq (snRNA-seq), we document chromatin accessibility and transcriptomic changes associated with the transition of hMuSCs to myotubes. Cancer secretome accelerated stem to myotube differentiation, altered the alternative splicing machinery and increased inflammatory, glucocorticoid receptor, and wound healing pathways in hMuSCs. Additionally, cancer secretome reduced metabolic and survival pathway associated miR-486, AKT, and p53 signaling in hMuSCs. hMuSCs underwent myotube differentiation when engrafted into NSG mice and thus providing a humanized in vivo skeletal muscle model system to study cancer cachexia.
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This study is a comparative analysis of the biochemical, hormonal, and mineral compositions of follicular fluid in preovulatory and cystic follicles of water buffalo (Bubalus bubalis). In total, reproductive tracts from 215 buffalo along with intact ovaries were collected randomly from an abattoir. The incidence of cystic conditions found in this study was 3.72% (8/215), involving the right ovary in 62.5% of instances and the left ovary in 37.5% of instances during the non-breeding season. Follicular fluid was aspirated from preovulatory follicles (12-15 mm diameter, oestrogen-active, follicular phase or stage IV corpus luteum on one of the two ovaries, n = 10) and cystic follicles (at least 20 mm diameter, no corpus luteum on any one of the two ovaries, n = 8). The follicular fluid samples were assayed for biochemical components (uric acid, creatinine, blood urea nitrogen, cholesterol, total protein, glucose, ascorbic acid, and alkaline phosphatase), hormones (progesterone, estradiol, and insulin), and minerals (calcium, magnesium, phosphorus, copper, zinc, and cobalt). Cystic follicles had greater (P < 0.05) concentrations of creatinine, blood urea nitrogen, cholesterol, progesterone, copper, zinc, and cobalt, and lesser (P < 0.05) concentrations of uric acid, glucose, ascorbic acid, estradiol, insulin, calcium, magnesium, and phosphorus compared with preovulatory follicles. These results indicated the marked differences in follicular fluid composition between preovulatory and cystic follicles in buffalo. Some of the changes were indicative of oxidative stress and disturbed steroidogenesis, two important mechanisms shown to be associated with cystic ovarian disease in various species. Further studies are warranted to investigate whether these differences are directly or indirectly involved in the formation of cystic follicles or are mere manifestations of the condition.