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Distal arthrogryposis type 5D (DA5D) is clinically characterized by knee extension contractures, distal joint contractures, clubfoot, micrognathia, ptosis, and scoliosis. We report nine affected individuals from eight unrelated Indian families with DA5D. Although the overall musculoskeletal phenotype is not very distinct from other distal arthrogryposis, the presence of fixed knee extension contractures with or without scoliosis could be an important early pointer to DA5D. We also report a possible founder variant in ECEL1 along with four novel variants and further expand the genotypic spectrum of DA5D. [ABSTRACT FROM AUTHOR]

Natural compounds such as polyphenols play several positive roles in maintaining the oxidative and inflammatory capacity of cells, which leads to their potential use as anticancer therapeutics. There is promising evidence for the in vitro and in vivo anticancer activity of many polyphenols, including resveratrol and quercetin, specifically in the treatment of colorectal cancer (CRC). There is a clear association between resveratrol and quercetin in interfering with the mechanistic pathways involved in CRC, such as Wnt, P13K/AKT, caspase-3, MAPK, NF-κB, etc. These molecular pathways establish the role of resveratrol and quercetin in controlling cancer cell growth, inducing apoptosis, and inhibiting metastasis. The major bottleneck in the progression of the use of resveratrol and quercetin as anticancer therapeutics is their reduced bioavailability in vivo because of their rapid metabolism in humans. Recent advancements in various nanotechnological formulations are promising for overcoming these bioavailability issues. Various nanoformulations of resveratrol and quercetin have shown an optimistic impact on reducing the solubility and improving the stability of resveratrol and quercetin in vivo. A combinatorial approach using nanoformulations of resveratrol with quercetin could potentially increase the impact of resveratrol in controlling CRC cell proliferation. This review discusses the mechanism of resveratrol and quercetin, the two bioactive polyphenolics, in colon cancer, with an emphasis on various types of nanoformulations of the two molecules targeting colon cancer. It also explores the synergistic effect of combining resveratrol and quercetin in various nanoformulations, targeting colon cancer. This research delves into the enhanced pharmacokinetics and potential chemotherapeutic benefits of these bioactive polyphenolics when used together in innovative ways. [ABSTRACT FROM AUTHOR]

Ewing sarcoma (ES) of the spine is a rare childhood cancer with sparse literature on treatment outcomes. We aimed to describe survival outcomes and prognostic factors in patients with spinal ES treated at a single institute in a resource-challenged setting. We conducted a retrospective analysis of patients with spinal ES registered at a tertiary care oncology center between 2003–2019. Clinical patient data was retrieved from hospital records. Cox regression analysis was used to identify the association of baseline clinical parameters with event free survival (EFS) and overall survival (OS). A cohort of 85 patients was analyzed including 38 (45%) patients with metastatic disease. The median age was 15 years with 73% being male. Local therapy was administered in 62 (72.9%) patients with surgery alone in 8 (9.4%), radiotherapy alone in 36 (42.4%) and both in 18 (21.2%) patients. A higher proportion of males received local therapy than females (80.3% versus 59.1%; p = 0.049). The median EFS and OS were 20.1 and 28.6 months, respectively. On univariable analysis, age ≤ 15 years, female sex, serum albumin ≤3.5 g/dL and hemoglobin ≤11 g/dL were associated with inferior EFS while younger age, female sex, hypoalbuminemia and metastatic disease were associated with inferior OS. On multivariable analysis, only hypoalbuminemia was predictive for inferior EFS (HR:2.41; p = 0.005) while hypoalbuminemia (HR:2.06;p = 0.033) and female sex (HR:1.83; p = 0.046) were associated with inferior OS. We concluded that hypoalbuminemia confers poor prognosis in ES spine. Survival outcomes are poorer in females treated in our setting, possibly due to prevailing sex-based biases. [ABSTRACT FROM AUTHOR]

The rice leaf folder, Cnaphalocrocis medinalis Gueee (Lepidoptera: Pyralidae), is major leaf feeding pest of rice, Oryza sativa L. (Poaceae), and is widely distributed throughout the rice producing countries in Asian, causing considerable yield losses. Cultivation of susceptible rice varieties is among the major reasons of insect pest outbreak. Contrary, growing resistant rice varieties plays a key role in keeping the insect pest population below economic threshold level. Growing resistant varieties is considered as safe and cost-effective method for the control of (RLF). Keeping in view the importance of the pest and economic value of the crop this experiment is designed to screen thirty five genotypes for resistance against rice leaf folder. These genotypes were evaluated for resistance against RLF in green house in the Department of Plant Breeding and Genetics, Agriculture University Peshawar, by following the method of Heinrichs et al. (1985). In our findings the screened genotypes falls in to different categories as 16 genotypes are highly susceptible, 6 are susceptible, 5 are moderately susceptible, 5 are moderately resistant, and only 3 tested genotypes proved resistance against the Cnaphalocrocis medinalis while none of the screened genotype falls in the category of highly resistance against RLF. These resistant genotypes can be used in future IPM program for the management of RLF. Furthermore, these resistant germplasms can be used in breeding programs for the development of high yielding resistant varieties against RLF. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive neurodegenerative disease that still has no permanent cure. The drugs prescribed in the present days are only for symptomatic relief for the patients. Many studies correlating the reduction in the incidence of AD with the diet consumed have been published. These studies showed that a diet rich in polyphenols is associated with a decrease in the incidence of AD. The present review is focused on the ability of pomegranate and its bioactive components to ameliorate the progression of AD and their ability to exert a neuroprotective effect. Various studies showing the ability of pomegranate in inhibiting enzymes, reducing reactive oxygen species, inhibition of microglial activation, inhibition of tau protein hyperphosphorylation, maintenance of synaptic plasticity, anti-inflammatory activity and its ability to inhibit Beta secretase-1 (BACE-1) has been reviewed in this article. In spite of the lack of studies on humans, there are compelling evidence indicating that pomegranate can reduce various risk factors involved in the causation of AD and thus can be used as a persistent nutraceutical to slow ageing and for providing neuroprotection for the treatment of AD. Highlights An overview of traditional and pharmacological uses of pomegranate (POM). Potential of POM in the treatment of neurodegenerative diseases especially in AD. Insight into the molecular mechanisms of neuroprotective effects of POM in AD. Clinical evaluation studies involving POM and its bioactive components. [ABSTRACT FROM AUTHOR]

The study aimes to investigate the physicochemical properties of seven honey samples to assess their quality as per GCC Standardization Organization (GSO) and international standard parameters. Seven honey samples, four marketed honey samples, and three locally produced Omani honey were collected and analysed for the pH, acidic content, % of insoluble matter, moisture content, proline, hydroxyl methyl furfural (HMF) and total reducing sugar contents. The results showed that pH of the tested honey samples are within the limit however acidity of the three samples did not comply with the prescribed limits. The moisture, proline, and hydroxy methyl furfural (HMF) contents of the honey samples tested are found to be within the acceptable range. However, the % of insoluble matter expressed for locally produced Sidr, Sumer, and Zah'r honey samples was below the maximum limit (0.5%) while marketed honey samples exceeded the limits of GSO (0.1%). The total reducing sugar concentration was below the limit in terms of four samples. Most of the tested honey samples meet the International/GSO standards for quality while a few failed to comply with acidity limits, the total reducing sugars content, and % of insoluble matter. [ABSTRACT FROM AUTHOR]

The sodium dependent SLC13 family transporters comprise of five genes SLC13A1, SLC13A2 (NaDC1), SLC13A3 (NaDC3), SLC13A4 and SLC13A5 (NaCT). Among them, NaDC1, NaDC3 and NaCT are sodium dependent transporters belonging to family of dicarboxylates (succinate, malate, α-ketoglutarate) and tricarboxylates (citrate). The mouse and the human NaCT structures have still not been crystallized, therefore structural information is taken from the related bacterial transporter of VcINDY. Citrate in the cytosol works as a precursor for the fatty acid synthesis, cholesterol, and low-density lipoproteins. The excess citrate from the matrix is translocated to the cytosol for fatty acid synthesis through these transporters and thus controls the energy balance by downregulating the glycolysis, tricarboxylic acid (TCA), and fatty acid breakdown. These transporters play an important role in regulating various metabolic diseases including cancer, diabetes, obesity, fatty liver diseases and CNS disorders. These di and tricarboxylate transporters are emerging as new targets for metabolic disorders such as obesity and diabetes. The mutation in the function of the NaCT causes several neurological diseases including neonatal epilepsy and impaired brain development whereas mutation of genes coding for citrate transport present in the liver may provide positive effect. Therefore, continued efforts from the earlier work on citrate transporters are required for the development of citrate inhibitors. This review discusses the structure, function, and regulation of the NaCT transporter. The review also highlights citrate role in diagnosing diseases such as cancer, diabetes, fatty liver, and diabetes. The therapeutic perspective of synthetic inhibitors against NaCT transporters is succinctly summarized. [ABSTRACT FROM AUTHOR]

Acyclovir (ACV) is a promising candidate for drug repurposing because of its potential to provide an effective treatment for viral infections and non-viral diseases, such as cancer, for which limited treatment options exist. However, its poor physicochemical properties limit its application. This study aimed to formulate and evaluate an ACV-loaded red clay nanodrug delivery system exhibiting an effective cytotoxicity. The study focused on the preparation of a complex between ACV and red clay (RC) using sucrose stearate (SS) (nanocomplex F1) as an immediate-release drug-delivery system for melanoma treatment. The synthesized nanocomplex, which had nanosized dimensions, a negative zeta potential and the drug release of approximately 85% after 3 h, was found to be promising. Characterization techniques, including FT-IR, XRD and DSC-TGA, confirmed the effective encapsulation of ACV within the nanocomplex and its stability due to intercalation. Cytotoxicity experiments conducted on melanoma cancer cell lines SK-MEL-3 revealed that the ACV release from the nanocomplex formulation F1 effectively inhibited the growth of melanoma cancer cells, with an IC50 of 25 ± 0.09 µg/mL. Additionally, ACV demonstrated a significant cytotoxicity at approximately 20 µg/mL in the melanoma cancer cell line, indicating its potential repurposing for skin cancer treatment. Based on these findings, it can be suggested that the RC-SS complex could be an effective drug delivery carrier for localized cancer therapy. Furthermore, the results of an in silico study suggested the addition of chitosan to the formulation for a more effective drug delivery. Energy and interaction analyses using various modules in a material studio demonstrated the high stability of the composite comprising red clay, sucrose stearate, chitosan and ACV. Thus, it could be concluded that the utilization of the red clay-based drug delivery system is a promising strategy to improve the effectiveness of targeted cancer therapy. [ABSTRACT FROM AUTHOR]

Pyrilla perpusilla (Walker) is one of the devastating pests which decrease yield directly and indirectly of sugarcane crop. For the safe management of P. perpusilla, field experiments were conducted to find the population of Pyrilla perpusilla on 12 different sugarcane varieties under field conditions at two different districts Charsadda and district Dera Ismail Khan of Khyber Pakhtunkhwa. Plot size 36×16 m (length × width) was selected in both localities for the cultivation of sugarcane varieties (CP77/400, Jhang 59, 2086, US-633, YT-55, CPF-252, CPF-246, CPF-251, CPF-247, CPF-250, CPF-248, and CPF-249) in Feb 2020. Each variety was planted in sub-plot size 3×2 meters having 3 rows and 5plants/row in randomized complete block design (RCBD) with three replications. The data was recorded from Mar-Nov from fresh and ratoon crops of the year 2020 and 2021, respectively. The leaves (top, middle, and bottom) of five plants in each subplot was observed randomly for data collection every fortnight in all replications. The total mean population of Pyrilla perpusilla (eggs cluster and nymphs/adults) was recorded from the leaves of the plants. The experimental results were of the view that could be used to conclude the research that the different varieties have different behaviour towards hosting the P. perpusilla. The population Pyrilla perpusilla (eggs clusters and nymphs/adults) were found highest on CPF-252 while least population of P. perpusilla was recorded on CPF-249 in both location and both years of the study (2020-2021) with its peak activity in the month of August. Significantly, positive correlation was recorded between P. perpusilla (eggs clusters and nymphs/adults) population infestation and average abiotic factors (temperature, humidity and rainfall). The correlation between leaf length and leaf width with P. perpusilla (eggs clusters and nymphs/adults) was significantly positive, the correlation of P. perpusilla (eggs clusters and nymphs/adults) with cane length was non-significant but positive while negative non-significant correlation was found between P. perpusilla (eggs clusters and nymphs/adults) population and cane diameter. The population of P. perpusilla on sugarcane variety CPF-249 was comparatively less which can be combine in future IPM programmes for the suppression of P. perpusilla infestation. [ABSTRACT FROM AUTHOR]