Photolysis of tolfenamic acid in aqueous and organic solvents: a kinetic study.

Tolfenamic acid (TA) is a non-steroidal anti-inflammatory drug that was studied for its photodegradation in aqueous (pH 2.0-12.0) and organic solvents (acetonitrile, methanol, ethanol, 1-propanol, 1-butanol). TA follows first-order kinetics for its photodegradation, and the apparent first-order rate constants (k obs) are in the range of 0.65 (pH 12.0) to 6.94 × 10-2 (pH 3.0) min-1 in aqueous solution and 3.28 (1-butanol) to 7.69 × 10-4 (acetonitrile) min-1 in organic solvents. The rate-pH profile for TA photodegradation is an inverted V (∧) or V-top shape, indicating that the cationic form is more susceptible to acid hydrolysis than the anionic form of TA, which is less susceptible to alkaline hydrolysis. The fluorescence behavior of TA also exhibits a V-top-shaped curve, indicating maximum fluorescence intensity at pH 3.0. TA is highly stable at a pH range of 5.0-7.0, making it suitable for formulation development. In organic solvents, the photodegradation rate of TA increases with the solvent's dielectric constant and solvent acceptor number, indicating solute-solvent interactions. The values of k obs decreased with increased viscosity of the solvents due to diffusion-controlled processes. The correlation between k obs versus ionization potential and solvent density has also been established. A total of 17 photoproducts have been identified through LC-MS, of which nine have been reported for the first time. It has been confirmed through electron spin resonance (ESR) spectrometry that the excited singlet state of TA is converted into an excited triplet state through intersystem crossing, which results in an increased rate of photodegradation in acetonitrile.

Undiagnosed vertebral fragility fractures in patients with distal radius fragility fractures: an opportunity for prevention of morbimortality in osteoporotic patients in developing countries.

Our study investigates vertebral fractures in individuals with distal radius fractures. Among 512 patients, 41.21% had vertebral fractures, predominantly in the lumbar spine. These findings highlight the importance of screening for vertebral fractures in this population, informing early intervention strategies to mitigate risks associated with osteoporosis. PURPOSE: This study's main goal was to look into the frequency, location, kind, and severity of asymptomatic vertebral fragility fractures (VFF) in people who had fractures of the fragility of the distal radius. Although VFF is frequently misdiagnosed, it is linked to higher mortality, morbidity, and hip fracture risk. The study also attempted to investigate the relationship between VFF and certain demographic and lifestyle factors, as well as FRAX data, in this patient population. METHODS: Between January, 2021, and January, 2022, individuals with low-energy distal radial fractures who presented to the emergency room of tertiary care hospital of Karachi, Pakistan, were the subject of a cross-sectional study and were 45 years of age or older except those who fitted the exclusion criteria (n = 208). The thoracic and/or lumbar spine was imaged using radiology, and information on demographics, way of life, and FRAX (Fracture Risk Assessment Tool) was gathered. Using the Genant semiquantitative approach, an impartial and blinded orthopaedist identified VF in the images and determined their severity. SPSS version 20 was used to analyse the data. RESULTS: Two hundred eleven (41.21%) of them were found to have radiographic VFF and only 12 (2.34%) of the 512 patients who were tested were getting osteoporotic therapy. The thoracic spine (32.7%), followed by the lumbar spine (43.12%), was the area most frequently afflicted. In 24.17% of the patients, multiple fractures of the thoracolumbar spine were found. The wedge form (54.5%), followed by biconcave (30.81%) and crush (14.7%), was the most prevalent VFF type. The majority of detected VFF were rated as having a 25-40% height loss (64.9%) then severe (> 40%) fractures (35.1%), according to the Genant grading method. Notably, there were no variations in smoking, drinking, BMI, or FRAX score between patients with and without VFF that were statistically significant. CONCLUSION: Based on our study's findings, it is clear that osteoporotic vertebral fragility fractures occur in almost half of individuals with distal radius fractures. The lumbar spine is notably the most affected region, predominantly with wedge fractures. Given the high prevalence of asymptomatic vertebral fragility fractures (VFF), proactive measures are necessary to mitigate associated risks. Prioritising comprehensive fall risk assessments for these patients and interventions to enhance bone mineral density and strength are crucial. Early identification of asymptomatic VFF enables timely intervention, optimising patient care and minimising the risk of complications in this vulnerable population.

Toxic elements identified in breast milk of mothers residing in water contaminated region of Sindh and their impact on infants' growth patterns: A case-control study.

Breast milk is a vital source of nutrition for breastfed infants, providing essential nutrients and elements but, in some cases, toxic ones. This is the first case-control study that investigated the elemental profile of breast milk samples collected from mothers residing in Matiari (Sindh), a region with insufficient industrial waste management, and its potential impact on infants' anthropometrics. Precisely, 62 milk samples, including 42 cases and 20 controls, were analyzed using the ICP-MS technique. Overall, six elements showed significance between the two groups, arsenic (As) was present at 0.68 µg/L in cases and absent in controls, while lead (Pb) exhibited elevated concentrations in the case group at 4.56 µg/L compared to 0.25 µg/L in controls, well-known for their toxicity. Barium (Ba) and manganese (Mn) levels were also higher in cases, associated with reported health effects on child well-being. Essential elements molybdenum (Mo) and selenium (Se) were higher in the controls. Furthermore, the association of these metals with the child growth standards as per WHO guidelines was calculated. Linear regression analysis revealed As negatively associated with WAZ and WHZ scores, while Mo was positively associated with WAZ, WHZ, and HAZ scores. These findings highlight serious health concerns in the region, where toxic elements pervade drinking water and food sources. Immediate actions are imperative to maintain the wellness of future generations.

Investigation of Pharmacologically Important Polyphenolic Secondary Metabolites in Plant-based Food Samples Using HPLC-DAD.

Polyphenolic compounds are vital components of plants. However, their analysis is particularly difficult and challenging due to their similar chemical and structural properties. In this study, we developed a simple and reproducible HPLC-DAD protocol for determining nineteen pharmacologically important polyphenols in plant-based food samples, including fruits (apple, banana, grapefruit, peach, grapes, plum, and pear), vegetables (onion, cabbage, capsicum, garlic, lemon, tomato, potato, and spinach), and other edible items (corn, kidney beans, green tea, black tea, and turmeric). The reference standards were pooled into four different groups based on logP values and expected retention time to avoid compound co-elution. These developed methods will be useful for the qualitative and quantitative analysis of biologically important polyphenolic compounds in various food samples and botanicals.

Poultry consumption and perceptions in Tehsil Shakargarh, Punjab, Pakistan: Implications for public health during COVID-19.

This study investigated the habits and attitudes of individuals towards poultry consumption, utilizing primary data collected through a survey of 5 households from 285 localities in Tehsil Shakargarh, Punjab, Pakistan (n = 1425). Household selection was randomized, and personal visits were conducted for data collection via formal interviews employing a structured questionnaire. Coordinates for each site were obtained using a Garmin eTrex device, in conjunction with meteorological data, to determine global positioning system (GPS) coordinates. A notable portion of respondents (38.8 %) possessed basic knowledge, while the majority (61.2 %) demonstrated intermediate knowledge regarding commercial broilers (chickens raised for meat production). A significant proportion (70.3 %) harbored misconceptions about the inclusion of hormones/antibiotics in poultry feed, with a minority (0.2 %) misinformed about broiler chickens' leg weakness. Some respondents (17.3 %) held both misconceptions, while others (12.2 %) had none. The majority (97.6 %) favored egg consumption, with 51.7 % preferring commercial chicken eggs and 48.3 % opting for domestic chicken eggs. Preference for white-colored eggs (51.5 %) slightly outweighed that for brown-colored eggs (48.5 %). A minority (1.3 %) speculated that poultry consumption could be a potential cause of COVID-19, while the majority (65.7 %) disagreed, and a portion (33.0 %) remained uncertain. Nearly all respondents (99.9 %) believed in the immunity-boosting properties of protein intake, with 65 % associating such benefits with poultry meat and eggs. Similarly, 99.7 % did not encounter difficulties in accessing poultry products during lockdowns. Approximately half (46.3 %) of respondents believed that consuming well-cooked and safely handled poultry meat was safe during outbreaks. Poultry meat and eggs emerged as potentially efficient sources of nutrition during the COVID-19 pandemic, especially for protein-deficient populations like Pakistan. Therefore, initiatives should focus on enhancing commercial poultry production and educating the populace about its advantages.

Recruitment, Retention, and Training of Citizen Scientists in Translational Medicine Research: A Citizen Science Initiative on Non-Alcoholic Fatty Liver Disease.

Citizen science is a participatory science approach in which members of the public (citizens) collaborate with scientists and professional researchers and become involved in research and innovation activities, resulting in the co-creation of scientific knowledge and innovation. Citizen science has been widely applied in research, particularly in the social sciences, environmental sciences, information and communication technologies, and public health. However, the application of this approach in clinical sciences, particularly in translational medicine research, is still nascent. This exploratory study involved members of the public (citizen scientists) in a translational medicine experiment on non-alcoholic fatty liver disease that incorporated a lifestyle and weight-loss intervention. The aim of this paper is to report successful methods and approaches for the recruitment, retention, and training of citizen scientists. For the citizen scientists' recruitment, online calls placed on the websites of our research project and biomedical research center and targeted emails were the most helpful. Of the 14 members of the public who expressed interest in our study, six were recruited as citizen scientists. Citizen scientists were mostly female (n = 5, 83%), white (n = 3, 50%), over 50 years of age (n = 4, 67%), educated to postgraduate level (n = 5, 83%), and either retired or not in employment (n = 5, 83%). The retention rate was 83% (n = 5), and the dropout rate was 17% (n = 1). We arranged instructor-led interactive online training sessions (an hour-long one-on-one session and two-hour group sessions). Research skills training covered ethics in research and qualitative and quantitative data analysis. Citizen scientists were given several incentives, such as reimbursement of travel and care costs, selection as citizen scientists of the month, publications of their blogs and perspective articles, and co-authorship and acknowledgement in papers and project deliverables. To conclude, members of the public (particularly middle-aged white women with postgraduate education) are interested in becoming citizen scientists in translational medicine research. Their retention rate is higher, and they can contribute to different research activities. However, they need training to develop their research skills and expertise. The training should be simple, comprehensive, and flexible to accommodate the schedules of individual citizen scientists. They deserve incentives as they work on a voluntary basis.

Temporal and differential proteomic profile of molecular mediators associated with chronic and acute wound healing.

The underlying pathophysiology of nonhealing chronic wounds is poorly understood due to the changes occurring at the gene level and the complexity arising in their proteomic profile. Here, we elucidated the temporal and differential profile of the normal and diabetic wound-healing mediators along with their interactions and associated pathways. Skin tissues corresponding to normal and diabetic wounds were isolated at Days 0, 3, 6, and 9 representing different healing phases. Temporal gene expression was analyzed by quantitative real-time PCR. Concurrently, differential protein patterns in the wound tissues were identified by Nano LC-ESI-TOF mass spectrometry and later confirmed by Western blot analysis. Gene ontology annotation, protein-protein interaction, and protein pathway analysis were performed using DAVID, PANTHER, and STRING bioinformatics resources. Uniquely identified proteins (complement C3, amyloid beta precursor protein, and cytoplasmic linker associated protein 2) in the diabetic wound tissue implied that these proteins are involved in the pathogenesis of diabetic wound. They exhibit enhanced catalytic activity, trigger pathways linked with inflammation, and negatively regulate wound healing. However, in the normal wound tissue, axin 1, chondroitin sulfate proteoglycan 4, and sphingosine-1-phosphate receptor were identified, which are involved in proliferation, angiogenesis, and remodeling. Our findings demonstrate the correlation between elevated gene expression of tumor necrosis factor-α, interleukin (IL)-1ß, and identified mediators: aryl hydrocarbon receptor nuclear translocator, 5'-aminolevulinate synthase 2, and CXC-family, that inflicted an inflammatory response by activating downstream MAPK, JAK-STAT, and NF-κB pathways. Similarly, in normal wound tissue, the upregulated IL-4 and hepatocyte growth factor levels in conjunction with the identified proteins, serine/threonine-protein kinase mTOR and peroxisome proliferator-activated receptor gamma, played a significant role in the cellular response to platelet-derived growth factor stimulus, dermal epithelialization, and cell proliferation, processes associated with the repair mechanism. Furthermore, Western blot analysis indicated elevated levels of inflammatory markers and reduced levels of proliferative and angiogenic factors in the diabetic wound.

Serum metallomics reveals insights into the associations of elements with the progression of preleukemic diseases toward acute leukemia.

Acute leukemia (AL) is a critical neoplasm of white blood cells with two main subtypes: acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). This study is focused on understanding the association of the preleukemic disease aplastic anemia (APA) with ALL and AML at metallomic level, using healthy subjects as a control. In this study, a validated and efficient inductively coupled plasma-mass spectrometry/MS-based workflow was employed to profile a total of 13 metallomic features. The study encompassed 41 patients with AML, 62 patients with ALL, 46 patients with APA, and 55 age-matched healthy controls. The metallomic features consisted of eight essential elements (Ca, Co, Cu, Fe, Mg, Mn, Se, and Zn) and five non-essential/toxic elements (Ag, Cd, Cr, Ni, and Pb). Six out of the 13 elements were found to be substantially different (P < .05) using absolute concentrations between serum samples of AL (ALL and AML) and preleukemia (APA) patients in comparison with healthy subjects. Elements including magnesium, calcium, iron, copper, and zinc were upregulated and only one element (chromium) was downregulated in serum samples of disease when compared with healthy subjects. Through the utilization of both univariate tests and multivariate classification modeling, it was determined that chromium exhibited a progressive behavior among the studied elements. Specifically, chromium displayed a sequential upregulation from healthy individuals to preleukemic disease (APA), and ultimately in patients diagnosed with ALL. Overall, metallomic-based biomarkers may have the utility to predict the association of APA with ALL.

Smartphone-Assisted EY@MOF-5-Based Dual-Emission Fluorescent Sensor for Rapid On-Site Detection of Daclatasvir and Nitenpyram.

Fluorescent metal-organic frameworks (MOFs) are promising sensing materials with tunable and robust structural properties and remarkable luminescent capabilities. In this study, a novel dual-emission fluorescent metal-organic framework (EY@MOF-5) composite is synthesized by a one-pot bottle-around-ship approach. Eosin Y (EY) is encapsulated in MOF-5 to enhance its fluorescence properties and selectivity, effectively addressing typical MOF-5 limitations. EY@MOF-5 serves as a versatile dual-functional fluorescent sensor for two different analytes, daclatasvir (DCT) and nitenpyram (NTP), showing an impressive linear range of 10-200 nM and 0.1-300 µM, with detection limits of 233 pM and 65 nM, respectively. The established method is ultrafast, highly sensitive, and extremely selective for DCT and NTP detection in complex biological and food samples. Fluorescence results are compared and validated with the recommended UPLC method. Then, a smartphone-integrated sensing system is introduced for on-site, real-time, and quantitative analysis of DCT and NTP. The smartphone-assisted intelligent sensing method manifests promising results for DCT and NTP monitoring in biological and food samples, demonstrating its promising potential for the on-site detection of biologically and environmentally significant analytes.

Introducing the Muzzammil classification for spoke wheel injuries in children to enhance injury assessment and treatment in developing countries.

Motorbike spoke wheel injuries (SWIs) among children are a notable public health concern, especially in low and middle-income regions. The primary objective of this study is to comprehensively examine the patterns of motorbike spoke wheel injuries (SWIs) in children. Additionally, the study introduces a novel classification system for these injuries. The implementation of this classification system aims to streamline the management of SWIs, making it more efficient and facilitating the development of standardized treatment protocols. This prospective observational study was conducted in the Accident and Emergency Department from January 2019 to 2021. Children < 14 years of age of either gender with foot and ankle injury due to motorbike spoke wheels as passengers and presenting within 3 days were included. The motorbike SWI was assessed for its location and classified by a new classification as Class I, Soft tissue injury without skin loss; Class II, Skin loss of more than 1 cm without underlying tissue involvement; Class III, Skin loss with underlying tissue involvement, this class is further divided on basis of underlying soft-tissue involvement; Class IV: mangled foot/toe. Management plan and outcome were noted. In our study158 children suffering from SWI were registered with a mean age of 6.2 ± 5.4 years, 127 (80.37%) males and 31 (19.62%) females. Class I injury was seen in 18 (11.39%) patients, class II in 69 (43.67%), and class III in 68 (43.03%) patients. Class III injuries were further subcategorized as follows: IIIT (Tendon) injuries, which accounted for 32 cases (20.25%); IIIB (Bone) injuries, with 29 cases (18.35%); and IIINV (Neurovascular) injuries, identified in 7 cases (4.43%). Class IV injuries were observed in 3 (1.8%) children. The flap was needed in 33 (20.88%) patients. There were no complications like flap necrosis or graft rejection. In this current study, a new classification system specific for a motorbike SWI has been introduced along with its application on children presenting at tertiary care hospital's emergency department. The application of the proposed classification will enable universal management guidelines for SWIs, especially in the Ino-Pak region where SWIs are common.

Effects of prenatal dichromatic light exposure on hatching results and post-hatch performance of Japanese quail.

Present study evaluated the effect of lighted incubation on pre- and post-hatch performance of Japanese quail. In a completely randomized design, 1200 eggs were evenly divided into 4 treatments groups having six replicates (each tray was considered as replicate), 50 eggs each. Different dichromatic lights (Green + Red; GR, Green + Blue; GB, and Blue + Red; BR) of 250 lux were provided during incubation for 12 h daily and effects of these lights very evaluated on hatching results and post-hatch growth. After hatch, 600 quail chicks were divided into 4 treatments, 6 replicates, and 25 birds each. Regarding hatching traits, better hatchability was found in the GR group compared to GB, BR, and dark group; while early embryonic mortality was lower in BR, GB, and dark group than GR; mid embryonic mortality was lower in dark group and late embryonic mortality was noted in the GR group than those of other treatment groups. In addition, moisture loss during incubation was minimum in BR and dark groups; however, chick spread was better in the GR group. In terms of growth performance, weight gain was better in the GR group; feed intake in dark, feed conversion ratio in BR, and livability were better in BR and GR group. In morphometrics, keel and shank length were higher in all the colored groups (GB, BR, and GR) whereas body length, wing spread, shank circumference, drumstick length, and circumference were higher in the GR group. Regarding serum chemistry, glucose, albumin, and globulin levels were higher in the GR group. It was concluded that under the experimental conditions, GR light at the prenatal stage to Japanese quail eggs positively influenced hatching performance and post-hatch growth.

Comparative evaluation of different moulting methods on productive performance, egg quality, and antibody response of leghorn hens.

The aim of the study was to compare three moulting procedures and their effect on productive performance, egg quality, and antibody response of leghorn hens. For this, a total of 324 laying hens were distributed into three treatment groups having 12 replicates of 9 birds each according to completely randomized design. Treatments consisted of three moulting procedures based on feed and light restriction. The targeted weight at the end of moulting was 1450-1470 g. As soon as the moulting procedure is complete, the comparative analysis of post-moult productive performance (feed intake, egg production, egg weight, egg mass, feed per dozen eggs, feed per kg egg mass, livability), egg quality characteristics (egg weight, egg length and width, shape index, surface area, volume, albumen height, weight, Haugh unit score, yolk width, height, index, egg shell pore number, shell weight, thickness, breaking strength), and antibody response against Newcastle disease and avian influenza (H-9) were evaluated. Birds subjected to moulting procedure 3 (8 days fasting and gradual decrease in light) showed improvement in productive performance, egg geometry and quality traits, and antibody response against Newcastle disease virus. Birds experienced moulting procedure 1 (11 days fasting) had improved feed intake, egg production, and livability. However, birds moulted with procedure 2 (6 days fasting) revealed intermediate result in all the studied parameters. In conclusion, moulting through feed and light restriction with 8 days fasting and gradual reduction in light has potential to improve performance of leghorn hens.

A Challenging Case of Adult-Onset Still's Disease Complicated by Macrophage Activation Syndrome With Multiorgan Failure.

Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disease that involves the excessive production of proinflammatory cytokines. Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening immune-mediated disorder that can be primary or secondary to malignancy, infections, and autoimmune diseases. We present an interesting case of a young female with adult-onset Still's disease that commenced during pregnancy. Whole-body fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) scan showed diffuse uptake in the spleen and bone marrow with widespread lymphadenopathy. During the delayed diagnostic process to exclude lymphoproliferative malignancy, she developed severe HLH/macrophage activation syndrome (MAS) with multiorgan failure. In this case report, we described the challenges faced during the diagnosis of AOSD. We also highlighted the importance of using clinical criteria to aid in the early diagnosis and management of AOSD patients and the role of FDG-PET/CT scans in patients with AOSD. Additionally, we discussed the management aspects for patients with macrophage activation syndrome.

Recent advancements in the fabrication and photocatalytic applications of graphitic carbon nitride-tungsten oxide nanocomposites.

The present review focuses on the widely used graphitic carbon nitride (g-C3N4)-tungsten oxide (WO3) nanocomposite in photocatalytic applications. These catalysts are widely employed due to their easy preparation, high physicochemical stability, nontoxicity, electron-rich properties, electronic band structure, chemical stability, low cost, earth-abundance, high surface area, and strong absorption capacity in the visible range. These sustainable properties make them predominantly attractive and unique from other photocatalysts. In addition, graphitic carbon nitride (g-C3N4) is synthesized from nitrogen-rich precursors; therefore, it is stable in strong acid solutions and has good thermal stability up to 600 °C. This review covers the historical background, crystalline phases, density-functional theory (DFT) study, synthesis method, 0-D, 1-D, 2-D, and 3-D materials, oxides/transition/nontransition metal-doped, characterization, and photocatalytic applications of WO3/g-C3N4. Enhancing the catalytic performance strategies such as composite formation, element-doping, heterojunction construction, and nanostructure design are also summarized. Finally, the future perspectives and challenges for WO3/g-C3N4 composite materials are discussed to motivate young researchers and scientists interested in developing environment-friendly and efficient catalysts.

Stearic Acid and CeO2 Nanoparticles Co-functionalized Cotton Fabric with Enhanced UV-Block, Self-Cleaning, Water-Repellent, and Antibacterial Properties.

Superhydrophobic cotton fabrics with multifunctional features are highly desired in domestic and outdoor applications. However, the short coating longevity and hazardous reagents significantly reduce their commercial-scale applications. Herein, we introduce CeO2 nanoparticles and stearic acid (SA) to develop a fluorine-free, durable superhydrophobic cotton fabric that mimics the lotus effect. The pristine cotton fabric is treated with APTES-functionalized CeO2 nanoparticles by immersion followed by a dip and drying treatment with a 2% myristic acid solution. This sequential process creates a stable superhydrophobic cotton fabric (SA/CeO2-cotton fabric) with a water contact angle of 158° and a water sliding angle of 5°. The results are attributed to the combined effect of CeO2 nanoparticles and stearic acid that enhances surface roughness and reduces surface sorption energy. APTES facilitates the durable attachment of CeO2 nanoparticles and stearic acid to the cotton fabric. The modified cotton fabric is characterized by advanced analytical tools, demonstrating enhanced superhydrophobicity, self-cleaning, and antiwater absorption properties. Additionally, it exhibits remarkable UV-blocking (UPF 542) and antibacterial properties. The designed superhydrophobic cotton fabric unveils good mechanical, thermal, and chemical durability. The proposed strategy is simple, green, and economical and can be used commercially for functional fabric preparation.

BCL11A-targeted γ-globin gene induction by triterpenoid glycosides of Fagonia indica: A preclinical scientific validation of indigenous herb for the treatment of ß-hemoglobinopathies.

Pharmacological induction of fetal hemoglobin has proven to be a promising therapeutic intervention in ß-hemoglobinopathies by reducing the globin chain imbalance and inhibiting sickle cell polymerization. Fagonia indica has shown therapeutic relevance to ß-thalassemia. Therefore, we study the ethnopharmacological potential of Fagonia indica and its biomarker compounds for their HbF induction ability for the treatment of ß-thalassemia. Here, we identify, compound 8 (triterpenoid glycosides) of F. indica. as a prominent HbF inducer in-vitro and in-vivo. Compound 8 showed potent erythroid differentiation, enhanced cellular proliferation, ample accumulation of total hemoglobin, and a strong notion of γ-globin gene expression in K562 cultures. Compound 8 treatment also revealed strong induction of erythroid differentiation and fetal hemoglobin mRNA and protein in adult erythroid precursor cells. This induction was associated with simultaneous downregulation of BCL11A and SOX6, and overexpression of the GATA-1 gene, suggesting a compound 8-mediated partial mechanism involved in the reactivation of fetal-like globin genes. The in vivo study with compound 8 (10 mg/kg) in ß-YAC mice resulted in significant HbF synthesis demonstrated by the enhanced level of F-cells (84.14 %) and an 8.85-fold increase in the γ-globin gene. Overall, the study identifies compound 8 as a new HbF-inducing entity and provides an early "proof-of-concept" to enable the initiation of preclinical and clinical studies in the development of this HbF-inducing agent for ß-thalassemia.

Association of lipid metabolism-related metabolites with overweight/obesity based on the FTO rs1421085.

Globally, obesity is a severe health issue. A more precise and practical approach is required to enhance clinical care and drug development. The FTO (fat mass and obesity-associated) gene variant rs1421085 is strongly associated with an increased susceptibility to obesity in numerous populations; however, the precise mechanism behind this association concerning metabolomics is still not understood. This study aims to examine the association between metabolites and obesity-related anthropometric traits based on the variant FTO rs1421085. This study was based on a case-control design involving a total of 542 participants including overweight/obese cases and healthy controls. The blood samples were collected from all the participants. The isolated serum samples were subjected to untargeted metabolomics using GC-MS. The isolated DNA samples were genotyped for the FTO rs1421085 variant. Initially, a total of 42 metabolites were identified on GC-MS, which were subjected to further association analyses. The study observed a significant association of two metabolites, glycerol and 2,3-dihydroxypropyl stearate with FTO gene variant rs1421085 and obesity-related anthropometric traits including % BF, WHtR, WC, and HC. The CT genotype of FTO rs1421085 may greatly increase the risk of overweight/obesity by changing the lipid metabolism-related metabolites. Therefore, this study highlights the significance of biochemical networks in the progression of obesity in carriers of the FTO rs1421085 risk genotype.

Targeted Analysis of Veterinary Drugs in Food Samples by Developing a High-Resolution Tandem Mass Spectral Library.

Veterinary drug residues present in foods can pose severe health threats to the population. The present study aims to develop a high-resolution mass spectral library of 158 veterinary drugs of 16 different classes for their rapid identification in food samples through liquid chromatography-high-resolution electrospray ionization-tandem mass spectrometry (LC-HR-ESI-MS/MS). Standard drugs were pooled according to their log P values and exact masses before analysis. Spectra were collected at system automated collision energy, i.e., of 25-60 eV and four predetermined collision energies (10, 20, 30, and 40 eV) for each compound using a schedule precursor list of [M + H]+, [M + Na]+, and [M + NH4]+ ions. The utility of the developed database was checked by analyzing food samples. A total of 17 veterinary drugs based on the reference standard retention times (RTs), HR-MS spectra, and MS/MS spectra were identified in the analyzed samples. Moreover, five veterinary drugs were selected for quantitative analysis, including doxycycline hyclate, lincomycin, sulfasalazine, moxifloxacin, and diphenoxylate, using liquid chromatography-ion trap mass-spectrometry (LC-IT-MS). Concentrations of the drug were obtained to vary from 0.0805 to 0.9731 mg/kg in food samples and were found to be exceeded in most of the cases as per the maximum residue levels described by Food and Agriculture Organization (FAO)/World Health Organization (WHO). The MS data were submitted to the MetaboLights online database (MTBLS2914). This study will help in the high-throughput screening of multiclass veterinary drugs in foodstuffs.

Structure elucidation of olasubscorpioside C, a new rotameric biflavonoid glycoside from the stem barks of Olax subscorpioidea (Oliv).

From the n-butanol soluble fraction of the ethanol extract of the medicinal plant Olax subscorpioidea, a previously unreported rotameric biflavonoid glycoside constituted of 4'-O-methylgallocatechin-(4α → 8)-4'-O-methylgallocatechin as aglycone named olasubscorpioside C (1) along with the known 4'-O-methylgallocatechin (2) were isolated. Their structures were determined on the basis of spectrometric and spectroscopic techniques including HRFABMS, 1 H and 13 C NMR, DEPT 135o , HSQC, HMBC, ROESY, and CD followed by comparison with the reported data.

Analysis of Tolfenamic Acid using a Simple, Rapid, and Stabilityindicating Validated HPLC Method.

BACKGROUND: Tolfenamic acid (TA) belongs to the fenamates class of non-steroidal anti-inflammatory drugs. Insufficient information is available regarding the availa-bility of a reliable and validated stability-indicating method for the assay of TA. OBJECTIVE: A relatively simple, rapid, accurate, precise, economical, robust, and stability-indicating RP-HPLC method has been developed to determine TA in pure and tablet dosage forms. METHODS: The method was validated according to the ICH guideline, and parameters like linearity, range, selectivity, accuracy, precision, robustness, specificity, and solution stability were determined. TLC and FTIR spectrometry were used to ascertain the purity of TA. The specificity was determined with known impurities and after performing forced degradation, while the robustness was established by Plackett-Burman's experimental design. The mobile phase used for the analysis was acetonitrile and water (90:10, v/v) at pH 2.5. The detection of the active drug was made at 280 nm using a C18 column (tR = 4.3 min.). The method's ap-plicability was also checked for the yellow polymorphic form of TA. RESULTS: The results indicated that the method is highly accurate (99.39-100.80%), precise (<1.5% RSD), robust (<2% RSD), and statistically comparable to the British Pharmacopoeia method with better sensitivity and specificity. CONCLUSION: It was observed that the stress degradation studies do not affect the method's accuracy and specificity. Hence the proposed method can be used to assay TA and its tablet dosage form.