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Alzheimer's disease (AD) is a diverse disease with a complex pathophysiology. The presence of extracellular β-amyloid deposition as neuritic plaques and intracellular accumulation of hyper-phosphorylated tau as neurofibrillary tangles remain the core neuropathologic criteria for diagnosing Alzheimer's disease. Nonetheless, several recent basic discoveries have revealed significant pathogenic roles for other essential cellular and molecular processes. Previously, there were not so many disease-modifying medications (DMT) available as drug distribution through the blood-brain barrier (BBB) is difficult due to its nature, especially drugs of polypeptides nature and proteins. Recently FDA has approved lecanemab as DMT for its proven efficacy. It is also complicated to deliver drugs for diseases like epilepsy or any brain tumor due to the limitations of the BBB. After the advancements in the drug delivery system, different techniques are used to transport the medication across the BBB. Other methods are used, like enhancement of brain blood vessel fluidity by liposomes, infusion of hyperosmotic solutions, and local intracerebral implants, but these are invasive approaches. Non-invasive approaches include the formulation of nanoparticles and their coating with polymers. This review article emphasizes all the above-mentioned techniques, procedures, and challenges to transporting medicines across the BBB. It summarizes the most recent literature dealing with drug delivery across the BBB., (© 2024. The Author(s).)

RNA silencing is an innate immune mechanism of plants against invasion by viral pathogens. Artificial microRNA (amiRNA) can be engineered to specifically induce RNA silencing against viruses in transgenic plants and has great potential for disease control. Here, we describe the development and application of amiRNA-based technology to induce resistance to soybean mosaic virus (SMV), a plant virus with a positive-sense single-stranded RNA genome. We have shown that the amiRNA targeting the SMV P1 coding region has the highest antiviral activity than those targeting other SMV genes in a transient amiRNA expression assay. We transformed the gene encoding the P1-targeting amiRNA and obtained stable transgenic Nicotiana benthamiana lines (amiR-P1-3-1-2-1 and amiR-P1-4-1-2-1). Our results have demonstrated the efficient suppression of SMV infection in the P1-targeting amiRNA transgenic plants in an expression level-dependent manner. In particular, the amiR-P1-3-1-2-1 transgenic plant showed high expression of amiR-P1 and low SMV accumulation after being challenged with SMV. Thus, a transgenic approach utilizing the amiRNA technology appears to be effective in generating resistance to SMV., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Fruits, vegetables, and other food items contain phytochemicals or secondary metabolites which may be considered non-essential nutrients but have medicinal importance. These dietary phytochemicals exhibit chemopreventive and therapeutic effects against numerous diseases. Polyphenols are secondary metabolites found in vegetables, fruits, and grains. These compounds exhibit several health benefits such as immune modulators, vasodilators, and antioxidants. This review focuses on recent studies on using dietary polyphenols to treat cardiovascular disorders, atherosclerosis, and vascular endothelium deficits. We focus on exploring the safety of highly effective polyphenols to ensure their maximum impact on cardiac abnormalities and discuss recent epidemiological evidence and intervention trials related to these properties. Kaempferol, quercetin, and resveratrol prevent oxidative stress by regulating proteins that induce oxidation in heart tissues. In addition, polyphenols modulate the tone of the endothelium of vessels by releasing nitric oxide (NO) and reducing low-density lipoprotein (LDL) oxidation to prevent atherosclerosis. In cardiomyocytes, polyphenols suppress the expression of inflammatory markers and inhibit the production of inflammation markers to exert an anti-inflammatory response. Consequently, heart diseases such as strokes, hypertension, heart failure, and ischemic heart disease could be prevented by dietary polyphenols.

Background: Dryopteris ramosa is used as an old treatment for several diseases. D. ramose fronds are eaten to treat gastrointestinal (GIT) issues and as an antibiotic. However, there is a dearth of literature justifying its traditional use. Aims and objectives : the current work used biological and molecular docking studies to support traditional usage and elucidate D. ramosa 's multitarget mechanism. Materials and methods: Bioactive compounds were docked in silico. Force displacement transducers coupled with a power lab data gathering system examined the effects of compounds on rabbit jejunum, trachea, and aorta tissues. Albino mice and rats were used for in vivo studies. Results: Bioactive compounds interacted with inflammation, asthma, and diarrhea genes, according to in silico studies. D. ramosa crude extract (Dr.Cr) calmed impulsive contractions and K+ (80 mM)-provoked contractions in the jejunum and tracheal tissue dose-dependently, showing the presence of the Ca++ channel-blocking (CCB) effect, further verified by the rightward parallel shift of CRCs equivalent to verapamil. Polarity-based fractionation showed spasmolytic activity in Dr.DCM and muscarinic receptors mediated spasmogenic activity in the Dr.Aq fraction. Dr.Cr vasoconstricted the aortic preparation, which was totally blocked by an angiotensin II receptor antagonist. This suggests that Dr. Cr's contractile effect is mediated through angiotensin receptors. In rats and mice, it showed anti-inflammatory and antidiarrheal action. Conclusion: This study supports the traditional medicinal uses of D. ramosa against GIT disorders and may be an important therapeutic agent in the future., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Type II diabetes mellitus and its related complications are growing public health problems. Many natural products present in our diet, including polyphenols, can be used in treating and managing type II diabetes mellitus and different diseases, owing to their numerous biological properties. Anthocyanins, flavonols, stilbenes, curcuminoids, hesperidin, hesperetin, naringenin, and phenolic acids are common polyphenols found in blueberries, chokeberries, sea-buckthorn, mulberries, turmeric, citrus fruits, and cereals. These compounds exhibit antidiabetic effects through different pathways. Accordingly, this review presents an overview of the most recent developments in using food polyphenols for managing and treating type II diabetes mellitus, along with various mechanisms. In addition, the present work summarizes the literature about the anti-diabetic effect of food polyphenols and evaluates their potential as complementary or alternative medicines to treat type II diabetes mellitus. Results obtained from this survey show that anthocyanins, flavonols, stilbenes, curcuminoids, and phenolic acids can manage diabetes mellitus by protecting pancreatic β-cells against glucose toxicity, promoting β-cell proliferation, reducing β-cell apoptosis, and inhibiting α-glucosidases or α-amylase. In addition, these phenolic compounds exhibit antioxidant anti-inflammatory activities, modulate carbohydrate and lipid metabolism, optimize oxidative stress, reduce insulin resistance, and stimulate the pancreas to secrete insulin. They also activate insulin signaling and inhibit digestive enzymes, regulate intestinal microbiota, improve adipose tissue metabolism, inhibit glucose absorption, and inhibit the formation of advanced glycation end products. However, insufficient data are available on the effective mechanisms necessary to manage diabetes.

Viral diseases of cultivated crops are often caused by virus spillover from wild plants. Tobacco ( N . tabacum ) is an important economic crop grown globally. The viral pathogens of tobacco are traditional major subjects in virology studies and key considerations in tobacco breeding practices. A positive-strand RNA virus, wild tomato mosaic virus (WTMV), belonging to the genus potyvirus in the family potyviridae was recently found to infect tobacco in China. In this study, diseased tobacco leaf samples were collected in the Henan Province of China during 2020-2021. Several samples from different locations were identified as WTMV positive. An infectious DNA clone was constructed based on one of the WTMV isolates. By using this clone, we found that WTMV from tobacco could establish infections on natural reservoir hosts, demonstrating a possible route of WTMV spillover and overwintering in the tobacco field. Furthermore, the WTMV infection was found to be accompanied by other tobacco viruses in the field. The co-inoculation experiments indicate the superinfection exclusion (SIE) between WTMV and other potyvirus species that infect tobacco. Overall, our work reveals novel aspects of WTMV evolution and infection in tobacco and provides an important tool for further studies of WTMV.

Glutathione (GSH) peroxidases (GPxs or GSHPx) and thioredoxin (Trx) peroxidases (TPxs) are two classes of peroxidases that catalyze the reduction of peroxides. GPxs and TPxs generally use GSH or Trx, respectively, to recycle the oxidized cysteine (Cys) residue in the protein. However, it is unclear why unlike human GPxs, the Schizosaccharomyces pombe Gpx1 (spGpx1) prefers Trx over GSH for recycling of the active-site peroxidatic Cys residue. Here, we compared spGpx1 and S. pombe Tpx1 (spTpx1) protein sequences with those of their respective homologs in Saccharomyces cerevisiae and humans. Our analysis revealed that like spTpx1, spGpx1 contains a pair of conserved Cys residues (Cys36 and Cys82). These two conserved Cys residues are named peroxidatic and resolving Cys residues, respectively, and are found only in GPxs and TPxs that prefer Trx as an electron donor. Our analysis suggested that Cys36 and Cys82 in spGpx1 are most likely to form a disulfide bond upon oxidation of Cys36. Molecular modelling predicted that a conformational change might be required for the formation of this disulfide bond. Evolutionary analysis suggested that fungal GPxs and TPxs are related by divergent evolution from a common ancestor. Our analyses support a prediction that while spGpx1 and spTpx1 are phylogenetically and functionally different, they evolved from a common ancestor and use a similar mechanism for recycling of the active-site peroxidatic Cys residue., (© 2022. The Author(s).)

Objective: The reorganization of cancer services and the increased work burden on health care providers during the COVID-19 pandemic are likely to be associated with significant negative psychological impact. The aim of this study is to evaluate the impact of COVID-19 pandemic on the psychological well-being of oncology clinicians in the Middle East and North Africa (MENA) region., Materials and Methods: We randomly invited 1500 oncology clinicians including medical oncologists, clinical oncologists, radiation oncologists and surgical oncologists from 17 countries in the MENA region to complete a web-based survey to determine the level of psychological stress during the COVID-19 pandemic from October 2020 to January 2021. The questionnaire was based on the Perceived Stress Scale (PSS), Generalized Anxiety Disorders Scale (GAD-7) and WHO Well-being Index (WHO-5). The data was analyzed using SPSS version 21 and the difference between groups was measured by t-test and ANOVA., Results: Overall, 520 (35%) clinicians including 368 (71%) males and 152 (29%) females participated in the survey with 247 (47%) participants between the ages of 36 to 45 years. Average score of 29.6 for males and 30.2 on PSS-10, indicative of high-perceived stress in both the genders. Compared to males, females had significantly higher anxiety levels on GAD-7 scale (p=.04), but this difference in stress level and well-being was not observed on PSS-10 (p=.134) and WHO -5 well-being index (p=.709). Clinicians of age 25-35 years had significantly higher anxiety levels on GAD-7 scale (p=.004) and higher stress on PSS (p=.000) as compared to other age groups. Age over 55 years was associated with lower levels of anxiety and stress on GAD-7 and PSS. Oncology clinicians working in public sector experienced significantly lower stress as compared to private sector on PSS scale (p=.041)., Conclusions: Anxiety and stress levels among oncology clinicians have significantly increased in COVID-19 pandemic in the MENA region. Females and young clinicians had higher anxiety and stress, while oncology clinicians over the age of 55 years and working in the public sector reported less stress and anxiety. The general wellbeing of clinicians was well preserved even in a highly stressful and anxious situation.

Objective: To compare the outcome of induction-remission in acute lymphoblastic leukaemia patients treated according to two different guidelines., Methods: The descriptive retrospective cohort study was conducted at The Children's Hospital Lahore, Pakistan, and comprised clinical information sheets of acute lymphoblastic leukaemia patients from September 2014 to August 2015. Data regarding demographics, risk categorisation, rapid early response and induction-remission assessment was collected separately for Group 1 patients treated with Lahore protocol and Group 2 patients using United Kingdom acute lymphoblastic leukaemia-2011 interim guidelines. Data was analysed using SPSS version 20.0., Results: Of the 98 patients who had a median age of 6.4 years (interquartile range: 1.5-16 years), 48(49%) were in Group 1 and 50(51%) in Group 2. There were 14(29%) patients with standard risk in Group 1 while 34(71%) were high-risk. The corresponding numbers in Group 2 were 30(60%) and 20(40%) in Group 2. Rapid early response was noted in 18(37.5%) patients in Group 1 and 11(28%) in Group 2. Remission was achieved in 38(79%) patients in Group 1 and 36(72%) in Group 2. There was significant association of rapid early response with induction-remission in Group 2 (p<0.05) but not in Group 1 (p>0.05)., Conclusions: Induction-remission rate was comparable in the two treatment groups, but significant association of rapid early response with induction-remission was observed only in patients treated using United Kingdom acute lymphoblastic leukaemia-2011 interim guidelines.

With cancer being the third leading cause of mortality in the United Arab Emirates (UAE), there has been significant investment from the government and private health care providers to enhance the quality of cancer care in the UAE. The UAE is a developing country with solid economic resources that can be utilized to improve cancer care across the country. There is limited data regarding the incidence, survival, and potential risk factors for cancer in the UAE. The UAE Oncology Task Force was established in 2019 by cancer care providers from across the UAE under the auspices of Emirates Oncology Society. In this paper we summarize the history of cancer care in the UAE, report the national cancer incidence, and outline current challenges and opportunities to enhance and standardize cancer care. We provide recommendations for policymakers and the UAE Oncology community for the delivery of high-quality cancer care. These recommendations are aligned with the UAE government's vision to reduce cancer mortality and provide high quality healthcare for its citizens.

Calcifying fibrous tumors (CFT) are rare benign tumors. They usually affect children and young adults and the incidence is equal in males and females. The usual clinical presentation is that of a painless mass. A computed tomography scan typically reveals a well-demarcated calcified lesion. CFT usually presents as a solitary mass and the commonest sites of occurrence are in soft tissues, the pleura, or the peritoneum. Multifocal occurrences at the same site have also been reported. The first case of CFT was reported in 1988. We present a rare case of multiple calcifying fibrous tumors at multiple sites in the same patient. To the best of our knowledge, this is the first ever reported case of multifocal CFT atsix different anatomical sites in one patient.

Lactuca serriola L. has traditionally been used in folkloric medicine to manage respiratory, gastrointestinal, and multiple other ailments. The present study was undertaken to explore the effect of methanol extract of L. serriola on isolated rabbit tissue preparations, that is, jejunum, trachea, and aorta in an attempt to validate its folkloric use in traditional medicine for gastrointestinal, respiratory, and vascular ailments. The application of the methanol extract to isolated rabbit jejunum preparations exhibited concentration-dependent spasmogenic effect (0.03 to 3.0 mg/mL), but interestingly further increase in concentration (5.0 mg/mL) resulted in complete spasmolytic effect. The pretreatment of the tissue preparations with atropine (0.1  μ M) caused the suppression of the contractile response. Moreover, the same extract also caused relaxation of K(+)-(80 mM) induced spastic contractions of isolated rabbit jejunum preparations (5.0 mg/mL) and shifted the Ca(++) dose response curves towards right at concentration range of 0.3-1.0 mg/mL. Similarly, the extract application to isolated rabbit tracheal preparations relaxed the carbachol-(1  μ M) induced (0.3-1.0 mg/mL) as well as K(+)-(80 mM) induced contractions (3.0 mg/mL). Furthermore, it relaxed the phenylephrine (1  μ M)-induced contractions in isolated rabbit aorta preparations (3.0 mg/mL) and K(+) (80 mM)-induced contractions (1.0 mg/mL). These effects were found comparable to that of dicyclomine, as an antagonist of muscarinic receptors as well as a possible Ca(++) channel blocker. The previously mentioned findings may partially justify the folkloric use of Lactuca serriola in the management of conditions pertaining to spasm of intestine, bronchioles, and vasculature.