Menstrual Practice Needs Scale short form (MPNS-SF) and rapid (MPNS-R): development in Khulna, Bangladesh, and validation in cross-sectional surveys from Bangladesh and Uganda.

OBJECTIVES: Develop and validate short and rapid forms of the 36-item Menstrual Practice Needs Scale (MPNS-36). DESIGN: Item reduction prioritised content validity and was informed by cognitive interviews with schoolgirls in Bangladesh, performance of scale items in past research and stakeholder feedback. The original MPNS-36 was revalidated, and short and rapid forms tested in a cross-sectional survey. This was followed by further tests of dimensionality, internal consistency and validity in multiple cross-sectional surveys. SETTING AND PARTICIPANTS: Short form (MPNS-SF) and rapid form (MPNS-R) measures were developed in a survey of 313 menstruating girls (mean age=13.51) in Khulna, Bangladesh. They were further tested in the baseline survey of the Adolescent Menstrual Experiences and Health Cohort, in Khulna, Bangladesh (891 menstruating girls, mean age=12.40); and the dataset from the MPNS-36 development in Soroti, Uganda (538 menstruating girls, mean age=14.49). RESULTS: The 18-item short form reflects the six original subscales, with the four core subscales demonstrating good fit in all three samples (Khulna pilot: root mean square error of approximation (RMSEA)=0.064, 90% CI 0.043 to 0.084, Comparative Fit Index (CFI)=0.94, Tucker-Lewis Index (TLI)=0.92. Cohort baseline: RMSEA=0.050, 90% CI 0.039 to 0.062, CFI=0.96, TLI=0.95. Uganda: RMSEA=0.039, 90% CI 0.028 to 0.050, CFI=0.95, TLI=0.94). The 9-item rapid form captures diverse needs. A two-factor structure was the most appropriate but fell short of adequate fit (Khulna pilot: RMSEA=0.092, 90% CI 0.000 to 0.158, CFI=0.93, TLI=0.89). Hypothesised associations between the MPNS scores and other constructs were comparable between the MPNS-36 and MPNS-SF in all populations, and replicated, with attenuation, in the MPNS-R. Internal consistency remained acceptable. CONCLUSIONS: The MPNS-SF offers a reliable and valid measure of adolescent girls' menstrual hygiene experience while reducing participant burden, to support implementation and improve measurement in menstrual health research. The MPNS-R provides a brief measure with poorer structural validity, suited to short surveys and including menstrual health within broader research topics.

Examining characteristics of those who receive pedorthic services: A clinical audit.

Diabetes-related foot complications, including neuropathic plantar forefoot ulcers, are a significant contributor to morbidity and increased healthcare costs. This retrospective clinical audit examines the characteristics of people accessing pedorthics services who are at risk of neuropathic plantar forefoot ulcer (re)occurrence and the pathways and funding models used to access these services. A clinical record audit was conducted on all patients accessing a pedorthics service who had diabetes and neuropathy with a history of plantar forefoot ulceration. The data included demographics, diabetes and neuropathy duration, main forefoot pathology and other comorbidity, footwear and insole interventions, and health fund access status. A total of 70 patient records were accessed, and relevant data was extracted. The mean age of participants was 64.69 (standard deviation (SD) 11.78) years; 61% were male and 39% female. Duration of diabetes ranged from one to 35 years, with a mean of 14.09 years (SD 6.58). The mean duration of neuropathy was 8.56 (SD 4.16) years. The most common forefoot conditions were bony prominences at 71% (n = 50), rigid flat foot and limited joint mobility (53%, n = 37), and hallux abductovalgus at 47% (n = 33). All participants had hyperkeratosis; 34% (n = 24) had forefoot amputation, and around 34% (n = 24) had a history of digital amputation. Various publicly funded packages and private health insurance were accessed. This study investigates the sociodemographic and medical profiles of individuals with diabetes-related foot complexities prone to neuropathic plantar forefoot ulcers. It is the first to examine patients receiving pedorthic services, informing practitioner surveys and preventive care strategies. Understanding patient characteristics aids in optimising multidisciplinary care and reducing ulcer incidence. Further studies are warranted to explore the field to establish an effective multidisciplinary care approach between medical professionals, podiatrists and pedorthists to optimise patient outcomes.

Endophyte mediated biocontrol mechanisms of phytopathogens in agriculture.

The global human population is growing and demand for food is increasing. Global agriculture faces numerous challenges, including excessive application of synthetic pesticides, emergence of herbicide-and pesticide-resistant pathogenic microbes, and more frequent natural disasters associated with global warming. Searches for valuable endophytes have increased, with the aim of making agriculture more sustainable and environmentally friendly. Endophytic microbes are known to have a variety of beneficial effects on plants. They can effectively transfer nutrients from the soil into plants, promote plant growth and development, increase disease resistance, increase stress tolerance, prevent herbivore feeding, reduce the virulence of pathogens, and inhibit the growth of rival plant species. Endophytic microbes can considerably minimize the need for agrochemicals, such as fertilizers, fungicides, bactericides, insecticides, and herbicides in the cultivation of crop plants. This review summarizes current knowledge on the roles of endophytes focusing on their mechanisms of disease control against phytopathogens through the secretion of antimicrobial substances and volatile organic compounds, and the induction of systemic resistance in plants. Additionally, the beneficial roles of these endophytes and their metabolites in the control of postharvest diseases in plants have been summarized.

Development and validation of a non-invasive method for quantifying amino acids in human saliva.

As an analytical matrix, saliva has superior characteristics than blood and urine. Saliva collection is, first and foremost, non-invasive, making it convenient, painless, and secure for more susceptible people. Second, it does not need professional training for medical personnel, resulting in cost-effectiveness and suitability for extensive collection in support of research. In this study, we developed a method and used it to quantify 13 salivary-free amino acid (SFAA) profiles to support the early clinical diagnosis of diseases using LC-MS/MS. Using an Intrada Amino Acid column (100 × 3 mm, 3 µm), chromatographic separation was accomplished with a binary gradient elution, and an electrospray ionisation source running in the positive ionisation mode was chosen for data collection using the multiple reaction monitoring (MRM) modes. Amino acids were extracted from saliva using acetonitrile. In the MRM mode, LODs and LOQs for ten amino acids were in the range of 0.06-2.50 µM and 0.19-7.58 µM, respectively, and those values were in the range of 1.00-3.00 µM and 3.00-8.50 µM, respectively, for three amino acids. Matrix-matched six-point calibration curves showed a linear correlation coefficient (r 2) of ≥0.998. Recovery experiments validated the method by spiking the control sample at three different concentration levels (5, 50 and 100 µM), and the accuracy level was 85-110%. Except for Thr and Ser, intra- (n = 3) and inter-day (n = 3) precision fell between 0.02 and 7.28. Salivary amino acids can serve as possible biomarkers for various malignancies, with fluctuations in body fluids being crucial for cancer diagnosis; therefore, examining amino acid patterns in saliva can assist in early cancer detection. LC-MS offers improved selectivity and sensitivity for non-derivatised amino acid analysis, surpassing conventional methods and offering proactive quality assurance, making it suitable for complicated sample matrices. These discoveries could be significant in investigating new pathways and cancer treatments and looking for possible AA biomarkers for other malignancies and diseases.

Zoonotic linkage and environmental contamination of Methicillin-resistant Staphylococcus aureus (MRSA) in dairy farms: A one health perspective.

Methicillin-Resistant Staphylococcus aureus (MRSA) is a ubiquitous public health challenge, with its prevalence in human, animal, and environmental interfaces posing significant concerns. This study aimed to characterize and detect the zoonotic linkages of MRSA within the cow-environment-human interfaces in dairy farms to address the One Health perspective. A comprehensive investigation, involving 636 samples (an equal number of raw milk and cow nasal swab samples, along with varying numbers of human nasal swab and environmental samples), revealed an overall MRSA prevalence of 13.4% (n = 271/636). Notably, environmental samples exhibited the highest prevalence (19.3%), emphasizing the potential role of farm surroundings in MRSA transmission, while the lowest prevalence was found in raw milk at 11.8% (n = 31/263). The prevalence in cow nasal swabs and human nasal swabs was 13.3% (n = 35/263) and 15.1% (n = 8/53), respectively. Multiplex PCR analysis revealed the presence of different Staphylococcal enterotoxin (SEa, SEb, SEc, and SEd), and exfoliative toxin-producing genes (Eta, Etb) within the MRSA isolates underlining their potential to induce public health threats. All MRSA isolates exhibited complete resistance to Oxacillin (100%) and Amoxicillin (100%), while the highest sensitivity was observed for Vancomycin (85.8%). Furthermore, these MRSA strains demonstrated varying degrees of resistance to other commonly used antimicrobial drugs, including Cefoxitin (75.3%), Ceftarolin (71.2%), Sulfamethoxazole-Trimethoprim (63.5%), Ciprofloxacin (60%), and Gentamicin (49.5%). Detection of MRSA in cow, human, and environmental samples within the same farm vicinity highlights the risk of zoonotic transmission of MRSA from cows to humans through environmental interfaces. Phylogenetic analysis of the mecA gene in MRSA isolates from all sources within the same farm revealed a high similarity index (>84%) among them suggesting a shared evolutionary origin. Moreover, the MRSA isolates from milk samples showed a close evolutionary relationship with isolates from Kenya and Brazil, while the isolates from humans and the environment displayed noticeable resemblance to isolates from several Asian countries. The findings emphasize the importance of collaborative efforts under the One Health framework to address this multifaceted issue and ensure the safety of our food supply and public health.

Prediction and assessment of deleterious and disease causing nonsynonymous single nucleotide polymorphisms (nsSNPs) in human FOXP4 gene: An in - silico study.

In humans, FOXP gene family is involved in embryonic development and cancer progression. The FOXP4 (Forkhead box protein P4) gene belongs to this FOXP gene family. FOXP4 gene plays a crucial role in oncogenesis. Single nucleotide polymorphisms are biological markers and common determinants of human diseases. Mutations can largely affect the function of the corresponding protein. Therefore, the molecular mechanism of nsSNPs in the FOXP4 gene needs to be elucidated. Initially, the SNPs of the FOXP4 gene were extracted from the dbSNP database and a total of 23124 SNPs was found, where 555 nonsynonymous, 20525 intronic, 1114 noncoding transcript, 334 synonymous were obtained and the rest were unspecified. Then, a series of bioinformatics tools (SIFT, PolyPhen2, SNAP2, PhD SNP, PANTHER, I-Mutant2.0, MUpro, GOR IV, ConSurf, NetSurfP 2.0, HOPE, DynaMut2, GeneMANIA, STRING and Schrodinger) were used to explore the effect of nsSNPs on FOXP4 protein function and structural stability. First, 555 nsSNPs were analyzed using SIFT, of which 57 were found as deleterious. Following, PolyPhen2, SNAP2, PhD SNP and PANTHER analyses, 10 nsSNPs (rs372762294, rs141899153, rs142575732, rs376938850, rs367607523, rs112517943, rs140387832, rs373949416, rs373949416 and rs376160648) were common and observed as deleterious, damaging and diseases associated. Following that, using I-Mutant2.0 and MUpro servers, 7 nsSNPs were found to be the most unstable. GOR IV predicted that these seven nsSNPs affect protein structure by altering the protein contents of alpha helixes, extended strands, and random coils. Following DynaMut2, 5 nsSNPs showed a decrease in the ΔΔG value compared with the wild-type and were found to be responsible for destabilizing the corresponding protein. GeneMANIA and STRING network revealed interaction of FOXP4 with other genes. Finally, molecular dynamics simulation analysis revealed consistent fluctuation in RMSD and RMSF values, Rg and hydrogen bonds in the mutant proteins compared with WT, which might alter the functional and structural stability of the corresponding protein. As a result, the aforementioned integrated comprehensive bioinformatic analyses provide insight into how various nsSNPs of the FOXP4 gene change the structural and functional properties of the corresponding protein, potentially proceeding with the pathophysiology of human diseases.

Comparative analysis of nutrient composition and antioxidant activity in three dragon fruit cultivars.

Dragon fruit has significant economic value in many countries due to has excellent nutritional content, health advantages, and adaptability to different climates, making it an important crop in the global fruit industry. This study aimed to gather comprehensive nutritional data on three dragon fruit cultivars by analysing the levels of micronutrients, fibre, carbohydrates, antioxidants, vitamins, and minerals in their pulps. Uniform dragon fruit samples underwent thorough analysis for proximate composition, mineral content, pigments, antioxidants, and vitamin C, with statistical methods used to assess significant differences among the parameters studied. The proximate composition analysis revealed significant differences among the three dragon fruit cultivars. Among the proximate components, protein (0.40 ± 0.02 g/100 g), moisture (91.33 ± 0.88%), crude fibre (0.32 ± 0.07 g/100 g), and ash (1.27 ± 0.09 g/100 g) were more abundant in Hylocereus costaricensis than in Hylocereus undatus and Hylocereus megalanthus. On the other hand, Hylocereus undatus had higher carbohydrate (17.02 ± 0.63 g/100 g) and energy (69.74 ± 2.44 kcal/100 g) contents. K (7.23 ± 0.35 mg/100 g), Ca (1.61 ± 0.13 mg/100 g), Fe (1.84 ± 0.05 mg/100 g), and Zn (0.37 ± 0.034 mg/100 g) are highly abundant in H. costaricensis. Additionally, Hylocereus costaricensis had the highest anthocyanin content (120.15 ± 3.29 mg/g FW) and total carotenoid content (72.51 ± 1.62 mg/g FW), along with the highest vitamin C content (8.92 ± 0.13 mg/g FW) and total soluble phenolic content (572.48 ± 20.77 mg/100 g). Its remarkable antioxidant activity was further highlighted by the lowest SC50 value (13.50 ± 0.4 mg/mL) for its DPPH radical scavenging capacity. The total soluble sugar content was highest in Hylocereus megalanthus (8.72 ± 0.30 g/100 g FW). Hierarchical clustering analysis revealed distinct trait and genotype associations; among the studied cultivars, Hylocereus costaricensis demonstrated superior performance across multiple traits. Correlation analysis indicated significant positive correlations among several traits, while principal component analysis highlighted the contribution of each trait to overall variance, with PC1 explaining 73.95% of the total variance. This study highlights the nutritional variations among dragon fruit cultivars, with Hylocereus costaricensis showing superior performance, guiding dietary planning and functional food development.

Alpha-Synuclein Interaction with UBL3 Is Upregulated by Microsomal Glutathione S-Transferase 3, Leading to Increased Extracellular Transport of the Alpha-Synuclein under Oxidative Stress.

Aberrant aggregation of misfolded alpha-synuclein (α-syn), a major pathological hallmark of related neurodegenerative diseases such as Parkinson's disease (PD), can translocate between cells. Ubiquitin-like 3 (UBL3) is a membrane-anchored ubiquitin-fold protein and post-translational modifier. UBL3 promotes protein sorting into small extracellular vesicles (sEVs) and thereby mediates intercellular communication. Our recent studies have shown that α-syn interacts with UBL3 and that this interaction is downregulated after silencing microsomal glutathione S-transferase 3 (MGST3). However, how MGST3 regulates the interaction of α-syn and UBL3 remains unclear. In the present study, we further explored this by overexpressing MGST3. In the split Gaussia luciferase complementation assay, we found that the interaction between α-syn and UBL3 was upregulated by MGST3. While Western blot and RT-qPCR analyses showed that silencing or overexpression of MGST3 did not significantly alter the expression of α-syn and UBL3, the immunocytochemical staining analysis indicated that MGST3 increased the co-localization of α-syn and UBL3. We suggested roles for the anti-oxidative stress function of MGST3 and found that the effect of MGST3 overexpression on the interaction between α-syn with UBL3 was significantly rescued under excess oxidative stress and promoted intracellular α-syn to extracellular transport. In conclusion, our results demonstrate that MGST3 upregulates the interaction between α-syn with UBL3 and promotes the interaction to translocate intracellular α-syn to the extracellular. Overall, our findings provide new insights and ideas for promoting the modulation of UBL3 as a therapeutic agent for the treatment of synucleinopathy-associated neurodegenerative diseases.

Unusual A(H1N7) influenza A virus isolated from free-range domestic ducks in Bangladesh, 2023.

In Bangladesh, free-range duck farms provide opportunities for the generation of novel influenza A viruses as evidenced by the emergence of an unusual A(H1N7) virus in 2023. Continued surveillance of such environments for the potential emergence of influenza A viruses with novel properties remains a priority.

Occupational hazards and risks among the women in fisher communities in Cox's Bazar and Chattogram, Bangladesh.

BACKGROUND: Women in the fisher communities in coastal regions of Bangladesh are engaged in a wide range of fishery activities. However, there is limited evidence available on the occupational hazards and risks experienced by them. METHOD: The study was conducted among fishing colonies in Cox's Bazar and Chattogram districts in Bangladesh. This was a cross-sectional study blending qualitative and quantitative approaches. The qualitative component comprised five focus group discussions to understand the occupational context, hazards, and risks faced by the fisherwomen, informing the questionnaire design for the subsequent survey. The quantitative survey involved a sample of 207 women from fisher communities, gathering socio-demographic information, occupational hazards, risks, and health and safety practices. FINDINGS: The study found a high occurrence of occupational hazards, health risks and limited availability of preventive measures among the women in fisher communities. Occupational hazards include physical safety hazards such as slippery surfaces and fish cutting instruments, and physical hazards like prolonged sun exposure and noise. Chemical hazards like pesticides and saltwater, ergonomic hazards such as prolonged uncomfortable posture and heavy lifting, and biological hazards including inadequate sanitation facilities were prevalent. The study also identified the potential occupational risks, and the outcomes resulting from the hazards, including injuries (87.44%), musculoskeletal conditions (69.08%), skin diseases/conditions (56.52%), eye complaints (33.82%), severe respiratory distress (24.15%) and high incidence of self-reported communicable diseases. Most women (78.26%) did not use personal protective equipment, and the majority (93.72%) lacked a workplace first aid kit. CONCLUSION: The study revealed a high prevalence of occupational hazards and health risks, including injuries and diseases, among Bangladeshi women in fisher communities with insufficient safety measures. Collaboration among government, NGOs, development partners, fisheries stakeholders, and the community is imperative for targeted training, innovative procedures, ergonomic solutions, provision of protective equipment, and advocacy to enhance the well-being of these women.

Passive Wireless Porous Biopolymer Sensors for At-Home Monitoring of Oil and Fatty Acid Nutrition.

Dietary oils─rich in omega-3, -6, and -9 fatty acids─exhibit critical impacts on health parameters such as cardiovascular function, bodily inflammation, and neurological development. There has emerged a need for low-cost, accessible method to assess dietary oil consumption and its health implications. Existing methods typically require specialized, complex equipment and extensive sample preparation steps, rendering them unsuitable for home use. Addressing this gap, herein, we study passive wireless, biocompatible biosensors that can be used to monitor dietary oils directly from foods either prepared or cooked in oil. This design uses broad-coupled split ring resonators interceded with porous silk fibroin biopolymer (requiring only food-safe materials, such as aluminum foil and biopolymer). These porous biopolymer films absorb oils at rates proportional to their viscosity/fatty acid composition and whose response can be measured wirelessly without any microelectronic components touching food. The engineering and mechanism of such sensors are explored, alongside their ability to measure the oil presence and fatty acid content directly from foods. Its simplicity, portability, and inexpensiveness are ideal for emerging needs in precision nutrition─such sensors may empower individuals to make informed dietary decisions based on direct-from-food measurements.

Crystallographic structure, antibacterial effect, and catalytic activities of fig extract mediated silver nanoparticles.

Silver nanoparticles (Ag NPs) play a pivotal role in the current research landscape due to their extensive applications in engineering, biotechnology, and industry. The aim is to use fig (Ficus hispida Linn. f.) extract (FE) for eco-friendly Ag NPs synthesis, followed by detailed characterization, antibacterial testing, and investigation of bioelectricity generation. This study focuses on the crystallographic features and nanostructures of Ag NPs synthesized from FE. Locally sourced fig was boiled in deionized water, cooled, and doubly filtered. A color change in 45 mL 0.005 M AgNO3 and 5 mL FE after 40 min confirmed the bio-reduction of silver ions to Ag NPs. Acting as a reducing and capping agent, the fig extract ensures a green and sustainable process. Various analyses, including UV-vis absorption spectrophotometry (UV), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), Field emission scanning electron microscopy (FESEM), Energy dispersive X-ray spectroscopy (EDX) and Transmission electron microscopy (TEM) were employed to characterize the synthesized nanoparticles, and Gas chromatography-mass spectrometry (GC-MS) analysis of the fig extract revealed the presence of eleven chemicals. Notably, the Ag NPs exhibited a surface plasmon resonance (SPR) band at 418 nm, confirmed by UV analysis, while FTIR and XRD results highlighted the presence of active functional groups in FE and the crystalline nature of Ag NPs respectively. With an average particle size of 44.57 nm determined by FESEM and a crystalline size of 35.87 nm determined by XRD, the nanoparticles showed strong antibacterial activities against Staphylococcus epidermidis and Escherichia coli. Most importantly, fig fruit extract has been used as the bio-electrolyte solution to generate electricity for the first time in this report. The findings of this report can be the headway of nano-biotechnology in medicinal and device applications.

Alfin-like (AL) transcription factor family in Oryza sativa L.: Genome-wide analysis and expression profiling under different stresses.

Oryza sativa L. is the world's most essential and economically important food crop. Climate change and ecological imbalances make rice plants vulnerable to abiotic and biotic stresses, threatening global food security. The Alfin-like (AL) transcription factor family plays a crucial role in plant development and stress responses. This study comprehensively analyzed this gene family and their expression profiles in rice, revealing nine AL genes, classifying them into three distinct groups based on phylogenetic analysis and identifying four segmental duplication events. RNA-seq data analysis revealed high expression levels of OsALs in different tissues, growth stages, and their responsiveness to stresses. RT-qPCR data showed significant expression of OsALs in different abiotic stresses. Identification of potential cis-regulatory elements in promoter regions has also unveiled their involvement. Tertiary structures of the proteins were predicted. These findings would lay the groundwork for future research to reveal their molecular mechanism in stress tolerance and plant development.

A systematic first-principles investigation of the structural, electronic, mechanical, optical, and thermodynamic properties of Half-Heusler ANiX (ASc, Ti, Y, Zr, Hf; XBi, Sn) for spintronics and optoelectronics applications.

This paper is the first to look at the structural, electronic, mechanical, optical, and thermodynamic properties of the ANiX (ASc, Ti, Y, Zr, Hf; XBi, Sn) half-Heusler (HH) using DFT based first principles method. The lattice parameters that we have calculated are very similar to those obtained in prior investigations with theoretical and experimental data. The positive phonon dispersion curve confirm the dynamical stability of ANiX (ASc, Ti, Y, Zr, Hf; XBi, Sn). The electronic band structure and DOS confirmed that the studied materials ANiX (ASc, Ti, Y, Zr, Hf; XBi, Sn) are direct band gap semiconductors. The investigation also determined significant constants, including dielectric function, absorption, conductivity, reflectivity, refractive index, and loss function. These optical observations unveiled our compounds potential utilization in various electronic and optoelectronic device applications. The elastic constants were used to fulfill the Born criteria, confirming the mechanical stability and ductility of the solids ANiX (ASc, Ti, Y, Zr, Hf; XBi, Sn). The calculated elastic modulus revealed that our studied compounds are elastically anisotropic. Moreover, ANiX (ASc, Ti, Y, Zr, Hf; XBi, Sn) has a very low minimum thermal conductivity (Kmin), and a low Debye temperature (θD), which indicating their appropriateness for utilization in thermal barrier coating (TBC) applications. The Helmholtz free energy (F), internal energy (E), entropy (S), and specific heat capacity (Cv) are determined by calculations derived from the phonon density of states.

Potential utilization of ferulic acid and its derivatives in the management of metabolic diseases and disorders: An insight into mechanisms.

Metabolic diseases are abnormal conditions that impair the normal metabolic process, which involves converting food into energy at a cellular level, and cause difficulties like obesity and diabetes. The study aimed to investigate how ferulic acid (FA) and its derivatives could prevent different metabolic diseases and disorders and to understand the specific molecular mechanisms responsible for their therapeutic effects. Information regarding FA associations with metabolic diseases and disorders was compiled from different scientific search engines, including Science Direct, Wiley Online, PubMed, Scopus, Web of Science, Springer Link, and Google Scholar. This review revealed that FA exerts protective effects against metabolic diseases such as diabetes, diabetic retinopathy, neuropathy, nephropathy, cardiomyopathy, obesity, and diabetic hypertension, with beneficial effects on pancreatic cancer. Findings also indicated that FA improves insulin secretion by increasing Ca2+ influx through the L-type Ca2+ channel, thus aiding in diabetes management. Furthermore, FA regulates the activity of inflammatory cytokines (TNF-α, IL-18, and IL-1ß) and antioxidant enzymes (CAT, SOD, and GSH-Px) and reduces oxidative stress and inflammation, which are common features of metabolic diseases. FA also affects various signaling pathways, including the MAPK/NF-κB pathways, which play an important role in the progression of diabetic neuropathy and other metabolic disorders. Additionally, FA regulates apoptosis markers (Bcl-2, Bax, and caspase-3) and exerts its protective effects on cellular destruction. In conclusion, FA and its derivatives may act as potential medications for the management of metabolic diseases.

N-Sulfonylphenoxazines as neuronal calcium ion channel blockers.

Neuropathic pain is a type of chronic pain, usually caused by nerve damage, that responds poorly to traditional pain therapies. The N-type calcium channel (CaV2.2) is a well-validated pharmacological target to treat this condition. In order to further improve the inhibition of the N-type calcium channel relative to previously described inhibitors, and also address their problematic instability in blood plasma, the development of N-sulfonylphenoxazines as new calcium channel inhibitors was pursued. A series of N-sulfonylphenoxazines bearing ammonium side chains were synthesised and tested for their ability to inhibit both CaV2.2 and CaV3.2 (T-type) neuronal ion channels. Compounds with low micromolar activity in CaV2.2 were identified, equivalent to the most effective reported for this class of bioactive, and calculations based on their physical and chemical characteristics suggest that the best performing compounds have a high likelihood of being able to penetrate the blood-brain barrier. Representative N-sulfonylphenoxazines were tested for their stability in rat plasma and were found to be much more resilient than the previously reported N-acyl analogues. These compounds were also found to be relatively stable in an in vitro liver microsome metabolism model, the first time that this has been investigated for this class of compound. Finally, molecular modelling of the CaV2.2 channel was used to gain an understanding of the mode of action of these inhibitors at a molecular level. They appear to bind in a part of the channel, in and above its selectivity filter, in a way that hinders its ability to undergo the conformational changes required to open and allow calcium ions to pass through.

Wildland firefighter work history and clinical indicators of cardiovascular health.

OBJECTIVE: To determine the association between the occupational history as a wildland firefighter (WFF) and clinical indicators of cardiovascular health. METHODS: Among 2,862 WFFs we evaluated associations between the number of total days assigned on fire and high-risk categories of three clinically measured cardiovascular indicators. RESULTS: Almost one-third (32%) of WFFs had one or more clinical measures that would place them in high-risk categories for BMI, blood pressure, and total cholesterol. WFF work history was associated with some of these measures: odds ratio (and 95% confidence interval) for highest versus lowest tertile of days on fire were 1.4 (1.2, 1.8) and 1.2 (1.0, 1.5) for high-risk categories of BMI and cholesterol, respectively. CONCLUSION: More frequent screening and targeted health promotion programs for WFFs are warranted to increase awareness of cardiovascular risk and prevention strategies.

Nucleic acid-binding KH domain proteins influence a spectrum of biological pathways including as part of membrane-localized complexes.

K-Homology domain (KH domain) proteins bind single-stranded nucleic acids, influence protein-protein interactions of proteins that harbor them, and are found in all kingdoms of life. In concert with other functional protein domains KH domains contribute to a variety of critical biological activities, often within higher order machineries including membrane-localized protein complexes. Eukaryotic KH domain proteins are linked to developmental processes, morphogenesis, and growth regulation, and their aberrant expression is often associated with cancer. Prokaryotic KH domain proteins are involved in integral cellular activities including cell division and protein translocation. Eukaryotic and prokaryotic KH domains share structural features, but are differentiated based on their structural organizations. In this review, we explore the structure/function relationships of known examples of KH domain proteins, and highlight cases in which they function within or at membrane surfaces. We also summarize examples of KH domain proteins that influence bacterial virulence and pathogenesis. We conclude the article by discussing prospective research avenues that could be pursued to better investigate this largely understudied protein category.

The experimental significance of isorhamnetin as an effective therapeutic option for cancer: A comprehensive analysis.

Isorhamnetin (C16H12O7), a 3'-O-methylated derivative of quercetin from the class of flavonoids, is predominantly present in the leaves and fruits of several plants, many of which have traditionally been employed as remedies due to its diverse therapeutic activities. The objective of this in-depth analysis is to concentrate on Isorhamnetin by addressing its molecular insights as an effective anticancer compound and its synergistic activity with other anticancer drugs. The main contributors to Isorhamnetin's anti-malignant activities at the molecular level have been identified as alterations of a variety of signal transduction processes and transcriptional agents. These include ROS-mediated cell cycle arrest and apoptosis, inhibition of mTOR and P13K pathway, suppression of MEK1, PI3K, NF-κB, and Akt/ERK pathways, and inhibition of Hypoxia Inducible Factor (HIF)-1α expression. A significant number of in vitro and in vivo research studies have confirmed that it destroys cancerous cells by arresting cell cycle at the G2/M phase and S-phase, down-regulating COX-2 protein expression, PI3K, Akt, mTOR, MEK1, ERKs, and PI3K signaling pathways, and up-regulating apoptosis-induced genes (Casp3, Casp9, and Apaf1), Bax, Caspase-3, P53 gene expression and mitochondrial-dependent apoptosis pathway. Its ability to suppress malignant cells, evidence of synergistic effects, and design of drugs based on nanomedicine are also well supported to treat cancer patients effectively. Together, our findings establish a crucial foundation for understanding Isorhamnetin's underlying anti-cancer mechanism in cancer cells and reinforce the case for the requirement to assess more exact molecular signaling pathways relating to specific cancer and in vivo anti-cancer activities.