A Study to Assess the Effectiveness of Buerger Allen Exercise on Lower Extremity Perfusion among Diabetes Mellitus patients admitted in Selected Hospital at Coimbatore

OBJECTIVES: 1. To assess the lower extremity perfusion among diabetes mellitus patient in experimental group and control group. 2. To evaluate the effectiveness of Buerger’s- Allen exercise inimproving the lower extremity perfusion among the experimental group. 3. To find out the association between interventional scores of Buerger’s- Allen exercise with selected demographic variables in experimental group and control group. An interventional study was conducted to evaluate the effect of buerger-allen exercise on lower extremity perfusion in patients with type II diabetes mellitus at risk of peripheral vascular disease. A Quasi experimental one group pretest-posttest group design was adopted. A purposive sample of 60 patients with type II diabetes mellitus patients at risk of peripheral vascular disease were selected for the study. The selected patients were assessed by Pain, Edema and Capillary Refill. The data was analyzed with descriptive and inferential statistical methods. The result revealed that there was a significant improvement in lower extremity perfusion after Buerger-Allen exercise. Hence, the study concluded that Buerger-Allen exercise was effective in improving the lower extremity perfusion in patients with type II diabetes mellitus at risk of peripheral vascular disease

COMPARATIVE DOCKING STUDIES ON THE EFFECT OF COMMERCIAL DRUGS ON DIPEPTIDYL PEPTIDASE-4 (DPP-4)

Objective: The aim of our study was to validate the accuracy of computational tools in drug discovery and molecular interaction studies by studying the inhibitory activity of various commercial drugs on DPP-4.Methods: In order to validate the accuracy of computational tools, 50 commercially available drugs were docked with DPP-4, a major target for type 2 diabetes treatment. Studies were performed using Discovery studio 3.5.Results: The analysis showed that out of the fifty selected drugs, 33 drugs passed the Lipinski's rule and commercially prescribed drugs namely Sulfonylurea, Pregabalin and Metaformin were found to have maximum interaction with the target.Conclusion: These major drugs which yielded the best results were found to be used in the treatment of diabetes which reconfirms the efficacy of these drugs, druggability of the target as well as the accuracy of the tool used

From Desert to Medicine: A Review of Camel Genomics and Therapeutic Products

Camels have an important role in the lives of human beings, especially in arid regions, due to their multipurpose role and unique ability to adapt to harsh conditions. In spite of its enormous economic, cultural, and biological importance, the camel genome has not been widely studied. The size of camel genome is roughly 2.38 GB, containing over 20,000 genes. The unusual genetic makeup of the camel is the main reason behind its ability to survive under extreme environmental conditions. The camel genome harbors several unique variations which are being investigated for the treatment of several disorders. Various natural products from camels have also been tested and prescribed as adjunct therapy to control the progression of ailments. Interestingly, the camel employs unique immunological and molecular mechanisms against pathogenic agents and pathological conditions. Here, we broadly review camel classification, distribution and breed as well as recent progress in the determination of the camel genome, its size, genetic distribution, response to various physiological conditions, immunogenetics and the medicinal potential of camel gene products

Complete genome sequence of Vibrio gazogenes PB1: an estuarine bacterium capable of producing prodigiosin from starch or cellulose

Vibrio is a genus of gram-negative, rod-shaped, motile bacteria commonly found in saltwater. One species in particular, Vibrio gazogenes PB1, sourced from an estuarine environment, is known to produce the secondary metabolite, prodigiosin. This high-value compound has potential uses as an antibiotic, a fungicide, and an anti-cancer agent. To further explore its metabolic and genetic features for biotechnological purposes, the complete genome sequence of V. gazogenes PB1 was determined by Illumina and Pacbio sequencing. Two chromosomes were assembled with a mean coverage of 293x. Chromosome 1 is 3.5 Mbp in size with 45.3% GC content and chromosome 2 is 1.2 Mbp in size with 45.1% GC content. The entire genome harbours 4178 genes, of which 3988 are protein-coding and 114 are RNA-coding. A total of 55 virulence-related genes, 38 antimicrobial resistance genes, 48 transposase sequences, 2 intact prophage regions, and 10 genomic islands were present within the genome. Six genes associated with the degradation of cellulose and starch were also identified within the genome. Four of them were strongly up-regulated, as confirmed by RT-qPCR, thus providing strong evidence for their involvement in starch and cellulose degradation. Quite importantly, we demonstrate for the first time that starch and cellulose is associated with the synthesis of prodigiosin in a native prodigiosin-producing bacterium. The prodigiosin titres obtained in the presence of cellulose were on par with glucose as the carbon source which lends further support in the use of V. gazogenes PB1 as a biotechnological host for prodigiosin production

Carnosol Is a Novel Inhibitor of p300 Acetyltransferase in Breast Cancer

Carnosol, a natural polyphenol abundant in edible plants such as sage, rosemary, and oregano, has shown promising anticancer activity against various types of cancers. Nonetheless, very little is known about its molecular mechanism of action or its downstream target(s). We have previously shown that carnosol inhibits cellular proliferation, migration, invasion, and metastasis as well as triggers autophagy and apoptosis in the highly invasive MDA-MB-231 breast cancer cells. Here, we report that carnosol induces histone hypoacetylation in MDA-MB-231 and Hs578T breast cancer cells. We show that, while carnosol does not affect HDACs, it promotes a ROS-dependent proteasome degradation of p300 and PCAF histone acetyl transferases (HATs) without affecting other HATs such as GCN5 and hMOF. Carnosol-induced histone hypoacetylation remains persistent even when p300 and PCAF protein levels were rescued from degradation by (i) the inhibition of the proteasome activity by the proteasome inhibitors MG-132 and bortezomib, and (ii) the inhibition of ROS accumulation by the ROS scavenger, N-acetylcysteine. In addition, we report that, in a cell-free system, carnosol efficiently inhibits histone acetyltransferase activity of recombinant p300 but not that of PCAF or GCN5. Molecular docking studies reveal that carnosol inhibits p300 HAT activity by blocking the entry of the acetyl-CoA binding pocket of the catalytic domain. The superimposition of the docked conformation of the p300 HAT domain in complex with carnosol shows a similar orientation as the p300 structure with acetyl-CoA. Carnosol occupies the region where the pantetheine arm of the acetyl-CoA is bound. This study further confirms carnosol as a promising anti-breast cancer therapeutic compound and identifies it as a novel natural p300 inhibitor that could be added to the existing panel of inhibitors.This work was supported by the Zayed Center for Health Sciences (ZCHS) research grant (Grant # 31R086) and by Al Jalila Foundation Research Grant (Grant # 21S102-AJF2018007)

Computational Modeling of the Interactions between DPP IV and Hemorphins

Type 2 diabetes is a chronic metabolic disorder characterized by high blood glucose levels due to either insufficient insulin production or ineffective utilization of insulin by the body. The enzyme dipeptidyl peptidase IV (DPP IV) plays a crucial role in degrading incretins that stimulate insulin secretion. Therefore, the inhibition of DPP IV is an established approach for the treatment of diabetes. Hemorphins are a class of short endogenous bioactive peptides produced by the enzymatic degradation of hemoglobin chains. Numerous in vitro and in vivo physiological effects of hemorphins, including DPP IV inhibiting activity, have been documented in different systems and tissues. However, the underlying molecular binding behavior of these peptides with DPP IV remains unknown. Here, computational approaches such as protein–peptide molecular docking and extensive molecular dynamics (MD) simulations were employed to identify the binding pose and stability of peptides in the active site of DPP IV. Findings indicate that hemorphins lacking the hydrophobic residues LVV and VV at the N terminal region strongly bind to the conserved residues in the active site of DPP IV. Furthermore, interactions with these critical residues were sustained throughout the duration of multiple 500 ns MD simulations. Notably, hemorphin 7 showed higher binding affinity and sustained interactions by binding to S1 and S2 pockets of DPP IV

Interactions of quercetin with receptor tyrosine kinases associated with human lung carcinoma

<p>Lung cancer is a deadly form of cancer with high morbidity and mortality rates. Deregulated receptor tyrosine kinases (RTKs) are frequently associated with the formation and development of lung carcinoma. Quercetin is a major dietary flavonoid that has been shown to induce cell growth inhibition and apoptosis in human lung cancer cell lines. In the current study, four major overexpressed RTKs – EGFR, FGFR1, IGF1R and c-Met – involved in human lung cancer were investigated. Molecular docking was employed to identify the binding orientation and inhibitory potential of quercetin in these RTKs. Quercetin bound to the ATP binding pocket of these kinases exhibited good binding scores and interactions by establishing hydrogen, hydrophobic and <i>π</i>-<i>π</i> interactions with the hinge region and the DFG motif in the activation loop. Thus, quercetin could be further explored as a platform for developing specific or polypharmacological compounds targeting overexpressed RTKs in lung cancer.</p

A Molecular Modeling Investigation of the Therapeutic Potential of Marine Compounds as DPP-4 Inhibitors

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by elevated levels of blood glucose due to insulin resistance or insulin-secretion defects. The development of diabetes is mainly attributed to the interaction of several complex pathogenic, genetic, environmental and metabolic processes. Dipeptidyl peptidase-4 (DPP-4) is a serine protease that cleaves X-proline dipeptides from the N-terminus of several polypeptides, including natural hypoglycemic incretin hormones. Inhibition of this enzyme restores and maintains glucose homeostasis, making it an attractive drug target for the management of T2DM. Natural products are important sources of bioactive agents for anti-T2DM drug discovery. Marine ecosystems are a rich source of bioactive products and have inspired the development of drugs for various human disorders, including diabetes. Here, structure-based virtual screening and molecular docking were performed to identify antidiabetic compounds from the Comprehensive Marine Natural Products Database (CMNPD). The binding characteristics of two shortlisted compounds, CMNPD13046 and CMNPD17868, were assessed using molecular dynamics simulations. Thus, this study provides insights into the potential antidiabetic activity and the underlying molecular mechanism of two compounds of marine origin. These compounds could be investigated further for the development of potent DPP-4 inhibitors

Key Features of Smart Medication Adherence Products: Updated Scoping Review

BackgroundOlder adults often face challenges in self-managing their medication owing to physical and cognitive limitations, complex medication regimens, and packaging of medications. Emerging smart medication dispensing and adherence products (SMAPs) offer the options of automated dispensing, tracking medication intake in real time, and reminders and notifications. A 2021 review identified 51 SMAPs owing to the rapid influx of digital technology; an update to this review is required. ObjectiveThis review aims to identify new products and summarize and compare the key features of SMAPs. MethodsGray and published literature and videos were searched using Google, YouTube, PubMed, Embase, and Scopus. The first 10 pages of Google and the first 100 results of YouTube were screened using 4 and 5 keyword searches, respectively. SMAPs were included if they were able to store and allowed for the dispensation of medications, tracked real-time medication intake data, and could automatically analyze data. Products were excluded if they were stand-alone software applications, not marketed in English, not for in-home use, or only used in clinical trials. In total, 5 researchers independently screened and extracted the data. ResultsThis review identified 114 SMAPs, including 80 (70.2%) marketed and 34 (29.8%) prototypes, grouped into 15 types. Among the marketed products, 68% (54/80) were available for consumer purchase. Of these products, 26% (14/54) were available worldwide and 78% (42/54) were available in North America. There was variability in the hardware, software, data collection and management features, and cost of the products. Examples of hardware features include battery life, medication storage capacity, availability of types and number of alarms, locking features, and additional technology required for use of the product, whereas software features included reminder and notification capabilities and availability of manufacturer support. Data capture methods included the availability of sensors to record the use of the product and data-syncing capabilities with cloud storage with short-range communications. Data were accessible to users via mobile apps or web-based portals. Some SMAPs provided data security assurance with secure log-ins (use of personal identification numbers or facial recognition), whereas other SMAPs provided data through registered email addresses. Although some SMAPs were available at set prices or free of cost to end users, the cost of other products varied based on availability, shipping fees, and subscription fees. ConclusionsAn expanding market for SMAPs with features specific to at-home patient use is emerging. Health care professionals can use these features to select and suggest products that meet their patients’ unique requirements