Understanding the Impact of SARS-CoV-2 on Lung Endothelial Cells: Brief Mechanisms Unveiled.

As the world grapples with the coronavirus-19 (COVID) pandemic, more reports are coming in regarding Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in endotheliopathy. It is a vascular condition in which endothelial cell injury or damage inflicts anatomical and functional changes in the endothelium, significantly impacting the physiological process and function. Previously, it was assumed that SARS-CoV-2 infects respiratory epithelial cells via spike glycoproteins present on the surface of the virus. However, severe cases and different autopsy studies described the clandestine role of this virus in infecting endothelial cells other than epithelial cells. It was observed that SARS-CoV-2 targets the pulmonary and extrapulmonary systems to damage the microvasculature and affect respiratory functioning, resulting in the onset of endotheliopathy, thrombosis, inflammation, pulmonary edema, and fibrosis. Such deleterious events are the consequence of the hyperactive immune response initiated by the SARS-CoV-2 infection, leading to pulmonary and extrapulmonary complications. However, the molecular mechanism behind endotheliopathy and other complications caused by this virus is elusive and will be unraveled by covering recent literature in this mini-review.

Correction to "Ion-Exchange Resin/Carrageenan-Copper-Based Nanocomposite: Artificial Neural Network, Advanced Thermodynamic Profiling, and Anticoagulant Studies".

[This corrects the article DOI: 10.1021/acsomega.4c01540.].

Short lifespan is one's fate, long lifespan is one's achievement: lessons from Daphnia.

Studies of longevity rely on baseline life expectancy of reference genotypes measured in standardized conditions. Variation among labs, protocols, and genotypes makes longevity intervention studies difficult to compare. Furthermore, extending lifespan under suboptimal conditions or that of a short-lived genotype may be of a lesser theoretical and translational value than extending the maximal possible lifespan. Daphnia is becoming a model organism of choice for longevity research complementing data obtained on traditional models. In this study, we report longevity of several genotypes of a long-lived species D. magna under a variety of protocols, aiming to document the highest lifespan, factors reducing it, and parameters that change with age and correlate with longevity. Combining longevity data from 25 experiments across two labs, we report a strong intraspecific variation, moderate effects of group size and medium composition, and strong genotype-by-environment interactions with respect to food level. Specifically, short-lived genotypes show no caloric restriction (CR) effect, while long-lived ones expand their lifespan even further under CR. We find that the CR non-responsive clones show little correlation between longevity and two measures of lipid peroxidation. In contrast, the long-lived, CR-responsive clones show a positive correlation between longevity and lipid hydroperoxide abundance, and a negative correlation with MDA concentration. This indicates differences among genotypes in age-related accumulation and detoxification of LPO products and their effects on longevity. Our observations support the hypothesis that a long lifespan can be affected by CR and levels of oxidative damage, while genetically determined short lifespan remains short regardless.

SARS-CoV-2-induced phosphorylation and its pharmacotherapy backed by artificial intelligence and machine learning.

Aims: To investigate the role of phosphorylation in SARS-CoV-2 infection, potential therapeutic targets and its harmful genetic sequences. Materials & Methods: Data mining techniques were employed to identify upregulated kinases responsible for proteomic changes induced by SARS-CoV-2. Spike and nucleocapsid proteins' sequences were analyzed using predictive tools, including SNAP2, MutPred2, PhD-SNP, SNPs&Go, MetaSNP, Predict-SNP and PolyPhen-2. Missense variants were identified using ensemble-based algorithms and homology/structure-based models like SIFT, PROVEAN, Predict-SNP and MutPred-2. Results: Eight missense variants were identified in viral sequences. Four damaging variants were found, with SNPs&Go and PolyPhen-2. Promising therapeutic candidates, including gilteritinib, pictilisib, sorafenib, RO5126766 and omipalisib, were identified. Conclusion: This research offers insights into SARS-CoV-2 pathogenicity, highlighting potential treatments and harmful variants in viral proteins.

This study explores the process called phosphorylation, which involves adding phosphate groups to certain proteins, influences the way the SARS-CoV-2 virus causes disease. The virus manipulates host enzymes to help it spread and survive. Researchers used data analysis techniques to identify the proteins that play a role in this process, aiming to find potential targets for treatments. They analyzed genetic sequences of key virus proteins and used various tools to predict harmful mutations. The study found several promising compounds that could be used to target the virus. Further research and experiments are needed to confirm their effectiveness as COVID-19 treatments.

This research explored the process called phosphorylation, which involves adding certain molecules to proteins, affects how the SARS-CoV-2 virus makes people sick. The virus uses our own cell's machinery to help it spread. Researchers used computer analysis to find out which proteins are involved in this process, hoping to find new ways to treat COVID-19. They studied the genetic code of important parts of the virus and used computer programs to predict if there were harmful changes in the code. They found some potential medicines that could be used to fight the virus and reduce its harm, but more research and testing are needed to be sure.

Ion-Exchange Resin/Carrageenan-Copper-Based Nanocomposite: Artificial Neural Network, Advanced Thermodynamic Profiling, and Anticoagulant Studies.

Carrageenan (CG) and ion exchange resins (IERs) are better metal chelators. Kappa (κ) CG and IERs were synthesized and subjected to copper ion (Cu2+) adsorption to obtain DMSCH/κ-Cu, DC20H/κ-Cu, and IRP69H/κ-Cu nanocomposites (NCs). The NCs were studied using statistical physics formalism (SPF) at 315-375 K and a multilayer perceptron with five input nodes. The percentage of Cu2+ uptake efficiency was used as an outcome variable. Via the grand canonical ensemble, SPF gives models for both monolayer and multilayer sorption layers. For in vitro anticoagulant activity (ACA), the activated partial thromboplastin time were calculated using 100 µL of rabbit plasma incubated at 37 °C. After 2 min, 100 L of 0.025 M CaCl2 was added, and the clotting time was recorded for each group (n = 6). The results demonstrated that the key covariables for the adsorption process were pH and concentration. The results of artificial neural network models were comparable with the experimental findings. The error rates varied between 4.3 and 1.0%. The prediction analysis results ranged from 43.6 to 89.2. The ΔG and ΔS values for IRP69H/κ-Cu obtained were -18.91 and -16.32 and 26.21 and 22.74 kJ/mol for the temperatures 315 and 345 K, respectively. Adsorbate species were perpendicular to the adsorbent surfaces, notwithstanding the apparent importance of macro- and micropore volumes. These adsorbents typically fluctuate with temperature changes and contain one or more layers of sorption. Negative and positive sorption energies correspond to endothermic and exothermic processes. The biosorption energy (E1 and E2) values in this experiment have a value of less than 23 kJ mol-1. Complex SPF models' energy distributions validate surface properties and interactions with adsorbates. At a concentration of 100 µg/mL, DC20H/κ-Cu2+ exhibited an ACA of only 8 s. These NCs demonstrated better greater ACA with the order DC20H/κ < DMSCH/κ < IRP69H/κ. More research is needed to rule out the chemical processes behind the ACA of CG/IER-Cu NCs.

Targeting Anti-Inflammatory Pathways to Treat Diabetes-Induced Neuropathy by 6-Hydroxyflavanone.

It is evident that inflammation and metabolic syndrome instigated by diabetes mellitus can precipitate diabetes-induced neuropathy (DIN) and pain. In order to find an effective therapeutic method for diabetes-related problems, a multi-target-directed ligand model was used. 6-Hydroxyflavanone (6-HF) carrying anti-inflammatory and anti-neuropathic pain potential due to its quadruplicate mechanisms, targeting cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX), and opioid and GABA-A receptors was investigated. The anti-inflammatory potential of the test drug was confirmed utilizing in silico, in vitro, and in vivo tests. A molecular simulation approach was utilized to observe the interaction of 6-HF with the inflammatory enzyme COX-2 as well as opioid and GABA-A receptors. The same was confirmed via in vitro COX-2 and 5-LOX inhibitory assays. In vivo tests were performed to analyze the thermal anti-nociception in the hot-plate analgesiometer and anti-inflammatory action in the carrageenan-induced paw edema model in rodents. The potential anti-nociceptive effect of 6-HF was evaluated in the DIN model in rats. The Naloxone and Pentylenetetrazole (PTZ) antagonists were used to confirm the underlying mechanism of 6-HF. The molecular modeling studies revealed a favorable interaction of 6-HF with the identified protein molecules. In vitro inhibitory studies revealed that 6-HF inhibited the COX-2 and 5-LOX enzymes significantly. The 6-HF at dosages of 15, 30, and 60 mg/kg substantially reduced heat nociception in a hot plate analgesiometer as well as carrageenan-induced paw edema in rodent models. The authors discovered that 6-HF had anti-nociception properties in a streptozotocin-induced diabetic neuropathy model. According to the findings of this study, 6-HF was demonstrated to diminish inflammation caused by diabetes as well as its anti-nociception effect in DIN.

Launching Liver Exchange and the First 3-Way Liver Paired Donation.

This article discusses the successful implementation of a liver exchange mechanism that led to 3 liver allotransplants and 3 hepatectomies between 3 incompatible patient-donor pairs.

Versatility of Hydrogels: From Synthetic Strategies, Classification, and Properties to Biomedical Applications.

Hydrogels are three-dimensional, cross-linked, and supramolecular networks that can absorb significant volumes of water. Hydrogels are one of the most promising biomaterials in the biological and biomedical fields, thanks to their hydrophilic properties, biocompatibility, and wide therapeutic potential. Owing to their nontoxic nature and safe use, they are widely accepted for various biomedical applications such as wound dressing, controlled drug delivery, bone regeneration, tissue engineering, biosensors, and artificial contact lenses. Herein, this review comprises different synthetic strategies for hydrogels and their chemical/physical characteristics, and various analytical, optical, and spectroscopic tools for their characterization are discussed. A range of synthetic approaches is also covered for the synthesis and design of hydrogels. It will also cover biomedical applications such as bone regeneration, tissue engineering, and drug delivery. This review addressed the fundamental, general, and applied features of hydrogels in order to facilitate undergraduates, graduates, biomedical students, and researchers in a variety of domains.

Surfactant free synthesis of cationic nano-vesicles: A safe triple drug loaded vehicle for the topical treatment of cutaneous leishmaniasis.

The basic aim of the study was to develop and evaluate the triple drug loaded cationic nano-vesicles (cNVs), where miltefosine was used as a replacement of surfactant (apart from its anti-leishmanial role), in addition to meglumine antimoniate (MAM) and imiquimod (Imq), as a combination therapy for the topical treatment of cutaneous leishmaniasis (CL). The optimized formulation was nano-sized (86.2 ±â€¯2.7 nm) with high entrapment efficiency (63.8 ±â€¯2.1% (MAM) and 81.4 ±â€¯2.3% (Imq)). In-vivo skin irritation assay showed reduced irritation potential and a decrease in the cytotoxicity of cNVs as compared to conventional NVs (having sodium deoxycholate as a surfactant). A synergistic interaction between drugs was observed against intracellular amastigotes, whereas the in-vivo antileishmanial study presented a significant reduction in the parasitic burden. The results suggested the potential of surfactant free, triple drug loaded cNVs as an efficient vehicle for the safe topical treatment of CL.

Plant-derived nanotherapeutic systems to counter the overgrowing threat of resistant microbes and biofilms.

Since antiquity, the survival of human civilization has always been threatened by the microbial infections. An alarming surge in the resistant microbial strains against the conventional drugs is quite evident in the preceding years. Furthermore, failure of currently available regimens of antibiotics has been highlighted by the emerging threat of biofilms in the community and hospital settings. Biofilms are complex dynamic composites rich in extracellular polysaccharides and DNA, supporting plethora of symbiotic microbial life forms, that can grow on both living and non-living surfaces. These enforced structures are impervious to the drugs and lead to spread of recurrent and non-treatable infections. There is a strong realization among the scientists and healthcare providers to work out alternative strategies to combat the issue of drug resistance and biofilms. Plants are a traditional but rich source of effective antimicrobials with wider spectrum due to presence of multiple constituents in perfect synergy. Other than the biocompatibility and the safety profile, these phytochemicals have been repeatedly proven to overcome the non-responsiveness of resistant microbes and films via multiple pathways such as blocking the efflux pumps, better penetration across the cell membranes or biofilms, and anti-adhesive properties. However, the unfavorable physicochemical attributes and stability issues of these phytochemicals have hampered their commercialization. These issues of the phytochemicals can be solved by designing suitably constructed nanoscaled structures. Nanosized systems can not only improve the physicochemical features of the encapsulated payloads but can also enhance their pharmacokinetic and therapeutic profile. This review encompasses why and how various types of phytochemicals and their nanosized preparations counter the microbial resistance and the biofouling. We believe that phytochemical in tandem with nanotechnological innovations can be employed to defeat the microbial resistance and biofilms. This review will help in better understanding of the challenges associated with developing such platforms and their future prospects.

In silico study of thymohydroquinone interaction with blood-brain barrier disrupting proteins.

AIM: To evaluate the inhibitory interaction of thymohydroquinone against blood-brain barrier (BBB)-associated neuropsychiatric and neurodegenerative disorders. MATERIALS & METHODS: An elaborated in silico study was designed to evaluate the interaction of thymohydroquinone with BBB-disrupting proteins and to highlight its pharmacokinetic and safety attributes. RESULTS: Thymohydroquinone demonstrated stable interaction with BBB-disrupting protein active site with Ki (inhibition constant) ranges of (2.71 mM-736.15 µM), binding energy (-4.3 to 5.6 Kcal/mol), ligand efficiency (-0.36 to 0.42 Kcal/mol) and root mean square deviation value of (0.80-2.59 Å). CONCLUSION: Further pharmacokinetic analysis revealed that thymohydroquinone is BBB and central nervous system (CNS) permeant with high acute toxicity and could be a candidate drug for the treatment of these neurological conditions.

Equilibrium, kinetics, thermodynamics and docking studies of Cu2+ ion adsorption over ion-exchange resin and kappa carrageenan blends in blood samples.

Cupric ions are hazardous to human beings and their removal from the body is very necessary. The blends of IRP69H (AMBERLITE IRP-69 [H+] RESIN), DC20H (DOWEX™ 20 [H+] Resin), DMSCH (DOWEX™ MARATHON™ MSC [H+] Resin) and Kappa Carrageenan (κ-) were utilized for the removal of ions of Cu2+ from the blood. They were subjected to docking studies which showed that there is no significant interaction with the blood albumin. IER dose of 0.5 mg/10mL of IRP69H/κ-, DMSCH/κ-, and DC20H/κ- was essential for the 2+ ion removal. At pH 5.4, optimal 2+ ions adsorption efficiency was attained. The adsorption capacities of 2+ were in the order of IRP69H/κ->DC20H/κ->DMSCH/κ-. While the data fitted well to Freundlich, Langmuir and Dubinin-Radushkevich. Pseudo-second order was followed for 2+ adsorption for DMSCH/κ- and DC20H/κ- while the pseudo-first order was demonstrated well for IRP69H/κ-.

Current Progress of Phytomedicine in Glioblastoma Therapy.

Glioblastoma multiforme, an intrusive brain cancer, has the lowest survival rate of all brain cancers. The chemotherapy utilized to prevent their proliferation and propagation is limited due to modulation of complex cancer signalling pathways. These complex pathways provide infiltrative and drug evading properties leading to the development of chemotherapy resistance. Therefore, the development and discovery of such interventions or therapies that can bypass all these resistive barriers to ameliorate glioma prognosis and survival is of profound importance. Medicinal plants are comprised of an exorbitant range of phytochemicals that have the broad-spectrum capability to target intrusive brain cancers, modulate anti-cancer pathways and immunological responses to facilitate their eradication, and induce apoptosis. These phytocompounds also interfere with several oncogenic proteins that promote cancer invasiveness and metastasis, chemotherapy resistance and angiogenesis. These plants are extremely vital for promising anti-glioma therapy to avert glioma proliferation and recurrence. In this review, we acquired recent literature on medicinal plants whose extracts/bioactive ingredients are newly exploited in glioma therapeutics, and also highlighted their mode of action and pharmacological profile.

Muslim Scholars' Knowledge, Attitudes and Perceived Barriers Towards Polio Immunization in Pakistan.

Pakistan is one of the two countries where polio remains endemic. Among multiple reasons of polio prevalence, false religious beliefs are accounted as major barriers towards polio immunization in Pakistan. Within this context, religious scholars are now engaged in polio immunization campaigns to dismantle the myths and battle the resurgence of polio in Pakistan. The objective of this study was to assess knowledge, attitudes and perceived barriers of Muslim scholars towards polio immunization in Pakistan. A descriptive, cross-sectional survey of Muslim scholars was conducted in Quetta and Peshawar divisions of Pakistan. From October to December 2015, a convenience sample of 770 Muslim scholars was recruited from the local mosques and religious institutions to participate in this study. Knowledge, attitudes, and perceived barriers were assessed by using self-administered, anonymous and pretested questionnaire. Descriptive and regression analyses were used to express the results with p < 0.05 taken as significant. Three hundred and forty-eight (45.2 %) participants exhibited good knowledge about polio with a mean score of 7.16 ± 2.12 (based on 14 questions). Knowledge gaps were identified about the transmission (32.6 %) and consequences of poliovirus (39.9 %). Overall, 527 (68.4 %) participants showed positive attitudes towards polio immunization with a mean attitude score of 27.35 ± 2.68 (based on nine statements). The majority of participants agreed on the need of depoliticizing polio immunization issues (87.1 %), while reservations were noted about their willingness to participate in future polio immunization programs (44.6 %). Security (75.8 %) and vaccine management issues (64 %) were reported by the participants as the major barriers towards polio immunization in Pakistan. The findings showed poor knowledge of Muslim scholars towards polio; however, their attitudes were positive towards polio immunization. More studies are required to assess the knowledge and attitudes of Muslim scholars at the national level to validate the findings of this study.

Short Communication: Evaluation of antimicrobial activities of Harmine, Harmaline, Nicotine and their complexes.

Harmine, Harmaline, Nicotine and its various complexes synthesized have been characterized by physical, spectral and analytical methods and curtained for in-vitro antimicrobial activity against different bacterial and fungal species at two different concentrations i.e.100µ/100µl and 200µ/100µl dose level respectively. Analysis showed that Nicotine, Zinc-Nico, Cd-Nico, Hg-Nico, Ni-Nico, Cu-Nico, Co-Nico, Harmine, and Harmaline having conc. of 100ug/ 100ul had antibacterial activity on zero, 5, 4, 10, zero, 5, 7, zero, zero strain of bacteria having an average of zero (SD=0.0000), 15.2000 (SD=1.30384), 18.2500 (SD=3.30404), 20.2000 (SD=1.39841), zero (SD=0.0000), 14.6000 (SD=0.89443), 15.8571 (SD=1.34519), zero (SD=0.0000), zero (SD=0.0000) respectively. Zinc (II) chloride, Cadmium (II) Iodide, Mercury (II) chloride, Nickel (II) chloride, Copper (II) chloride, Cobalt (II) chloride, Mercury (II) chloride, Mercury (II) harmine, Mercury (II) harmaline at 100ug/100ul is valid for 7, 8, 9, 2, 7, 8, 9, 10, 8 strains of bacteria with an average of 7.1429 (SD=1.06904), 10.0000 (SD=5.01427), 14.8889 (SD=6.00925), 6.0000 (SD=0.0000), 8.5714 (SD=4.27618), 8.2500 (SD=0.88641), 14.8889 (SD=6.00925), 18.6000 (SD=2.45855), 18.5000 (SD=1.85164) respectively. The above given compounds at the conc. of 200 µ/100ul is valid for 10, 9, 10, 8, 8, 10, 10, 10, 10 strains of bacteria with an average of 8.1 (SD=1.66333), 11.7778 (SD=5.28625), 16.1000 (SD=6.36745), 6.5000 (SD=0.92582), 9.7500 (SD=4.43203), 9.9000 (SD=2.76687), 16.1000 (SD=6.36745), 22.0000 (SD=2.44949), 20.4000 (SD=2.75681) respectively. The above given compounds at conc. of 200 µ/100ul showed antibacterial action on 3, 8, 8, 10, 3, 9, 8, zero, 3 strains of bacteria with an average of 14(SD=0.000), 16.8750 (SD=1.35620), 18.2500 (SD=3.45378), 22.7000 (SD=1.82878), 14.3333 (SD=0.57735), 16.7778 (SD=1.71594), zero (SD=0.000), 12.0000 (SD=1.00000) respectively. Hence according to the average value of the zone of inhibition, maximum antibacterial activity at 100-200ug/100ul is of Hg-Nico and Mercury salt; Mercury (II) harmine having an average of 20.2000 (SD=1.39841)-22.7000 (SD=1.82878) and 18.6000 (SD=2.45855)-22.0000 (SD=2.44949). Minimum antibacterial activity at 100-200ug/100ul is Nicotine100, Nicotine-Nico100, Harmine 100,Harmaline 100, Harmine 200 having zero average (SD=0.000).

A Cross-Sectional Survey of Healthcare Workers on the Knowledge and Attitudes towards Polio Vaccination in Pakistan.

INTRODUCTION: Pakistan accounts for 85.2% of the total polio cases reported worldwide. Healthcare workers (HCWs) are an integral part of immunization campaigns and source of education for the general public. This study aimed to assess the knowledge and attitudes towards polio vaccination among HCWs providing immunisation and education to general public in Quetta and Peshawar divisions of Pakistan. METHODS: A cross-sectional survey of 490 HCWs was conducted in two major referral public teaching hospitals of Quetta and Peshawar divisions. During February to April, 2015, a random sample of 490 HCWs was invited to participate in this study. Knowledge and attitudes were assessed by using self-administered, anonymous and pretested questionnaire. Descriptive and logistic regression analyses were used to express the results. RESULTS: A total of 468 participants responded to the questionnaire, giving a response rate of 95.5%. Overall, participants demonstrated good knowledge and positive attitudes towards polio vaccination. The mean knowledge score of HCWs about polio was 13.42 ± 2.39 (based on 18 knowledge questions) while the mean attitude score was 28.75 ± 5.5 (based on 9 attitudes statements). Knowledge gaps were identified about the incubation period of poliovirus (19.5%), management issues (31.9%), use of polio vaccine in mild illnesses (34.7%) and the consequences of the polio virus (36.9%). The majority of participants agreed that all children should be vaccinated for polio (95.1%), while reservations were noted about the need of a booster (38.9%), and sterility issues associated with polio vaccines (43.6%). Internet (n = 167, 37%) and Posters (n = 158, 35%) were the main sources used by HCWs to educate themselves about polio. CONCLUSION: Participants in this study had good knowledge and positive attitudes towards polio vaccination. Although the data are indicative of gaps in the knowledge of HCWs, the findings may not be generalized to other hospitals in Pakistan.

Knowledge, attitudes and perceptions towards polio immunization among residents of two highly affected regions of Pakistan.

BACKGROUND: Despite the efforts of national and international organizations, polio has not been eradicated from Pakistan. The prevalence of polio in Pakistan is exceptional in global context. Quetta and Peshawar divisions are amongst the most affected regions hit by polio in Pakistan. This study was carried out to assess the knowledge, attitudes and perceptions towards polio immunization among residents of Quetta and Peshawar divisions in Pakistan. METHODS: A descriptive, cross-sectional study involving 768 participants was conducted from August to December, 2014 in Quetta and Peshawar divisions in Pakistan. Multistage sampling technique was used to draw a sample of residents from each division. A pre-tested, self-administered questionnaire was used to collect the data from eligible participants. Descriptive and logistic regression analyses were used to express the results. RESULTS: A total of 38.8 % participants exhibited good knowledge about polio. Mean knowledge score of the participants was 7.35 ± 2.54 (based on 15 knowledge questions). Older age (p < 0.001), low qualification (p < 0.05), rural locality (p < 0.05) and Quetta division (p < 0.001) were significantly associated with poor knowledge of polio. A large proportion of participants displayed negative attitudes towards polio immunization (84.8 %), with a mean score of 19.19 ± 2.39 (based on 8 attitude statements). Lack of education (p < 0.001) and rural residence (p < 0.001) were significantly associated with the negative attitudes of participants towards polio immunization. False religious beliefs (39.06 %), lack of knowledge (33.7 %), fear of infertility by polio vaccines (32.16 %) and security issues (29.42 %) were reported by the participants as the main barriers towards polio immunization. CONCLUSION: The findings of this study showed poor knowledge and negative attitudes of participants towards polio immunizations. Religious beliefs and lack of knowledge about polio immunization were reported as the major barriers towards polio immunization.