In-silico screening of phytomolecules against multiple targets for wound management.

Chronic wound healing, especially in burns, is a major medical challenge with limited treatments. This study employs computational tools to identify phytomolecules that target multiple pathways involved in wound healing. By utilizing shape analysis, molecular docking, and binding energy calculations, potential compounds are pinpointed,to address the growing problem of chronic wounds. Initially, a set of phytomolecules from the ZINC database of natural molecules was screened to find compounds with shapes similar to well-known wound healing phytomolecules like curcumin, chromogenic acid, gallic acid, and quercetin. The most promising phytomolecules identified through shape similarity were further studied through molecular docking studies on several key targets involved in wound healing, including TNF-α, FGF, and TGF-ß. Among the tested phytomolecules, a ligand known as Fluorophenyl(5-(5-chloro-1-(2-fluorophenyl)-2-oxopentyl)-4,5,6,7-tetrahydrothieno[3,2c]pyridine-2-yl acetate) exhibited a strong affinity with favourable binding interactions for TNF-α ( - 7.1 kcal/mole), FGF (-6.9 kcal/mole), and TGF-ß (-5.1 kcal/mole). Another compound, 2,4 methoxybenzylidene-(-3)-oxo-2,3-dihydro-1-benzofuran-6-yl-4-methoxybenzoate, demonstrated a strong affinity with low binding energy for TNF-α ( - 6.8 kcal/mole) and FGF ( - 7.0 kcal/mole) targets. Isosakuranetin and Ermanin displayed moderate affinity for both TNF-α and FGF, with the highest affinity observed for the TGF-ß target. These findings suggest that these identified phytomolecules hold promise as potential lead compounds for further structural modifications, with the goal of designing new molecules that can target multiple pathways involved in the wound healing process.

Rapid scan white light two-dimensional electronic spectroscopy with 100 kHz shot-to-shot detection.

We demonstrate an approach to two-dimensional electronic spectroscopy (2DES) that combines the benefits of shot-to-shot detection at high-repetition rates with the simplicity of a broadband white light continuum input and conventional optical elements to generate phase-locked pump pulse pairs. We demonstrate this through mutual synchronization between the laser repetition rate, the acousto-optical deflector, the pump delay stage, and the CCD line camera, which allows for rapid scanning of pump optical delay synchronously with the laser repetition rate, while the delay stage is moved at a constant velocity. The resulting shot-to-shot detection scheme is repetition rate scalable and only limited by the CCD line rate and the maximum stage velocity. Using this approach, we demonstrate the measurement of an averaged 2DES absorptive spectrum in as much as 1.2 s of continuous sample exposure per 2D spectrum. We achieve a signal-to-noise ratio of 6.8 for optical densities down to 0.05 with 11.6 s of averaging at 100 kHz laser repetition rate. Combining rapid scanning of mechanical delay lines with shot-to-shot detection as demonstrated here provides a viable alternative to acousto-optic pulse shaping approaches that is repetition-rate scalable, has comparable throughput and sensitivity, and minimizes sample exposure per 2D spectrum with promising micro-spectroscopy applications.

Surface Geometry of Cargo-less Gold Nanoparticles Is a Driving Force for Selective Targeting of Activated Neutrophils to Reduce Thrombosis in Antiphospholipid Syndrome.

Antiphospholipid syndrome (APS) is an autoimmune disease characterized by recurrent arterial, venous, and microvascular thrombosis where activated neutrophils play a determinant role. However, neutrophils are challenging to target given their short lifespan in circulation and spontaneous activation. Screening of a small library of gold nanoparticles (AuNPs) led to the discovery of a formulation capable of targeting activated neutrophil attachment and has demonstrated that star-shaped, anti-PSGL-1-antibody-coated AuNPs (aPSGL-1-AuNPs) were more efficacious compared with other shapes of AuNPs. Our findings further revealed an exciting and safe targeting mode toward activated neutrophils in the APS mouse model induced by human-patient-derived antiphospholipid IgGs. Our studies demonstrate that targeting is dependent on the specific topographical features of the highly segregated PSGL-1 on the activated neutrophil surface for which a high affinity shape-driven nanomedicine can be designed and implemented. As such, star-shaped aPSGL-1-AuNPs serve as a promising nanoimmunotherapy for immunothrombosis associated with neutrophil adhesion in APS.

Unveiling the role of gut dysbiosis in non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a multifactorial complicated condition, reflected by the accumulation of extra fat in the liver. A detailed study of literature throws light on the fascinating connection between gut dysbiosis and NAFLD. The term 'gut dysbiosis' describes an imbalance in the harmony and operation of the gut microflora, which can upshoot a number of metabolic disorders. To recognize the underlying mechanisms and determine treatment options, it is essential to comprehend the connection between gut dysbiosis and NAFLD. This in-depth review discusses the normal gut microflora composition and its role in health, alterations in the gut microflora composition that leads to disease state focusing on NAFLD. The potential mechanisms influencing the advent and aggravation of NAFLD suggested disturbance of microbial metabolites, changes in gut barrier integrity, and imbalances in the composition of the gut microflora. Furthermore, it was discovered that gut dysbiosis affected immune responses, liver inflammation, and metabolic pathways, aggravating NAFLD.

Herbal-Based Dressings in Wound Management.

Wound management is one of the major global challenges in recent times, and woundassociated infection has a significant impact on the healthcare economy worldwide. Wounds can be acute or chronic type, also diabetic, trauma, accidental, burn wounds and minor cuts, bruises, and rashes, etc. One of the primary treatment options available in these conditions are the use of suitable dressing materials to cover the wound and accelerate the healing process. Since ancient times, according to archaeological theories, medicinal plants and oils have been employed for the treatment of wounds. Today researchers across the globe are focusing their efforts on fabrication of novel dressing materials that can provide the most effective treatment, easy exchange of nutrients, and absorb exudate from the wounds. Very lately, various research groups are also concentrating on the design and development of herb-loaded wound dressings, as herbal preparations contain numerous phytoconstituents with a broad spectrum of pharmacological properties when compared to synthetic drugs and also due to the perceived notion that herbal products are generally safe, even when administered over prolonged periods. They contain numerous bioactive that can act on the various phases of the wound healing process, providing an ideal environment for the healing process. The present review discusses the numerous approaches that are employed for the preparation of dressing materials incorporated with plant-derived phytoconstituents/extracts. This review also provides an insight into the healing process and wound healing agents derived from medicinal plants and oils. The review can serve as a database for researchers working in this field and can help them to select the most appropriate dressing material for the effective delivery of herbal preparations in the management of wounds.

Effect of herbal formulation on glimepiride pharmacokinetics and pharmacodynamics in nicotinamide-streptozotocin-induced diabetic rats.

BACKGROUND: Traditional medicinal herbs are widely consumed in developing countries to treat diabetes as they are perceived to be safer, less expensive, and have fewer side effects as compared to the conventional medicines. Diabecon (DB), Himalaya Herbal Healthcare, India is herbal over-the-counter formulation which contains several herbs that are reported in the traditional texts for the treatment of diabetes. The majority of these herbs have been investigated and found to interfere with the cytochrome pathway. The most common oral antihyperglycemic drug used today in clinical practice is Glimepiride (GP).The CYP2C9 enzyme is mainly responsible for the metabolism of GP. Herein we hypothesize that the co-administration of GP with DB may result in possible Herb-Drug Interactions (HDIs) as DB has the potential to significantly inhibit the CYP2C9 enzyme. OBJECTIVE: In the current study, the pharmacokinetic and pharmacodynamic interactions of GP (0.82 mg/kg) with DB (110.95 mg/kg) was investigated in diabetes induced (Nicotinamide-STZ) rats by co-administering both drugs orally for 21 days. MATERIALS AND METHODS: For the study of the HDI, Bioanalytical RP-HPLC/PDA method for quantifying GP in plasma of rats was developed and validated as per US-FDA guidelines. In vivo pharmacokinetic and pharmacodynamic parameters were studied on day 1 and day 21 post administration. RESULTS: The RP-HPLC/PDA method was successfully employed for quantification of GP in the PK studies. The co-administration of GP and DB in diabetic rats resulted in beneficial pharmacodynamic interactions, but there were no notable changes in the pharmacokinetic parameters of GP. CONCLUSION: This current investigation in an animal model suggests that co-administration of GP and DB may have significant therapeutic benefits in the treatment of diabetes; however, additional research, randomized clinical trials or case studies in humans, is needed.

A targetable pathway in neutrophils mitigates both arterial and venous thrombosis.

Arterial and venous thrombosis constitutes a major source of morbidity and mortality worldwide. Long considered as distinct entities, accumulating evidence indicates that arterial and venous thrombosis can occur in the same populations, suggesting that common mechanisms are likely operative. Although hyperactivation of the immune system is a common forerunner to the genesis of thrombotic events in both vascular systems, the key molecular control points remain poorly understood. Consequently, antithrombotic therapies targeting the immune system for therapeutics gain are lacking. Here, we show that neutrophils are key effectors of both arterial and venous thrombosis and can be targeted through immunoregulatory nanoparticles. Using antiphospholipid antibody syndrome (APS) as a model for arterial and venous thrombosis, we identified the transcription factor Krüppel-like factor 2 (KLF2) as a key regulator of neutrophil activation. Upon activation through genetic loss of KLF2 or administration of antiphospholipid antibodies, neutrophils clustered P-selectin glycoprotein ligand 1 (PSGL-1) by cortical actin remodeling, thereby increasing adhesion potential at sites of thrombosis. Targeting clustered PSGL-1 using nanoparticles attenuated neutrophil-mediated thrombosis in APS and KLF2 knockout models, illustrating the importance and feasibility of targeting activated neutrophils to prevent pathological thrombosis. Together, our results demonstrate a role for activated neutrophils in both arterial and venous thrombosis and identify key molecular events that serve as potential targets for therapeutics against diverse causes of immunothrombosis.

Teriparatide Associated Late Hypercalcemia: A Report of Two Cases and Literature Review.

Introduction: Teriparatide, recombinant human parathyroid hormone (1-34), is a safe and usually well-tolerated medication. We describe two cases of late-onset hypercalcemia associated with teriparatide use and report current evidence of hypercalcemia during the treatment with PTH analogs. Case report: Case 1 is a 54-year-old man with a history of osteoporosis, previously treated with 6 months of teriparatide, but had not been consistent in taking the medication. Before restarting teriparatide, his serum calcium, PTH and vitamin D were normal. Six months into the treatment, he developed asymptomatic hypercalcemia of 11.2 mg/dL 24 h after the last dose. Repeat serum calcium was normal and treatment was continued. Case 2 is a 75-year old woman with a history of osteopenia and severe scoliosis. Before starting teriparatide, her calcium, PTH and vitamin D were normal. Six months into the treatment, she developed asymptomatic hypercalcemia of 12.5 mg/dL. Teriparatide was held and subsequently her serum calcium normalized. Discussion: Transient hypercalcemia can occur during treatment with teriparatide and usually resolves within 16 h after administration. Late hypercalcemia, occurring more than 24 h after the dose, is rarely seen. It is usually mild, asymptomatic and rarely occurs repeatedly. Hypercalcemia occurs more often in patients with pre-existing hypercalcemia or vitamin D deficiency. It is rarely a cause of treatment disruption (0.18-4%). Conclusion: Clinicians should be aware of this side effect, especially in patients who may be at risk of complications of hypercalcemia.

The co-adsorption of thymohydroquinone dimethyl ether (THQ) and coumarin present in the aqueous extract of Ayapana triplinervis on mild steel and its protection in hydrochloric acid up to 323 K: computational and physicochemical studies.

This study evaluates the corrosion inhibition property of the aqueous and alcoholic leaf extracts of the medicinal plant Ayapana triplinervis. The major components in the extracts are thymohydroquinone dimethyl ether (THQ) and coumarin. It is clear from the weight-loss studies that the water extract of the leaves (AYW) is superior to the alcoholic extract (AYA) in terms of offering corrosion inhibition. The 96% efficiency of 4% (v/v) AYW in 0.5 N HCl at room temperature changes to 84.62% at 323 K. The mixed-type inhibition behaviour of AYW shows slight dominance in the anodic direction. Studies suggest the multilayer adsorption of phytochemicals on the metal surface and that the adsorption follows the Temkin model. Theoretical studies using DFT and BIOVIA Materials Studio investigations establish THQ as a good inhibitor with high adsorption characteristics. Even though the concentration of coumarin in the extract is low, its presence in the extract facilitates the adsorption of THQ on the metal surface, which is evident from the MD simulation study. The changes in the surface topography and elemental composition of the metal specimen in the inhibited and uninhibited solution are monitored by SEM and EDX spectral studies. XPS data support the presence of both THQ and coumarin on the metal surface and the existence of co-ordinate bonding between the metal's d orbital and the O atoms of THQ. Theoretical and experimental studies support the mixed mode of adsorption of THQ as physisorption followed by chemisorption.

Herbal Oils for Treatment of Chronic and Diabetic Wounds: A Systematic Review.

BACKGROUND: In the present scenario, diabetes is a growing health challenge, and its occurrence is growing across the globe. Diabetes, with its complications like diabetic wounds, vasculopathy, neuropathy, wound infections, and oxidative stress, is a serious cause of mortality worldwide. INTRODUCTION: Among the various complications, treatment of diabetic foot and ulcers is one of the major concerns in patients who are suffering from diabetes. The causative factors for this condition include increased oxidative stress, high blood glucose levels, vascular insufficiency, and microbial infections, and many a time, if left untreated, it may even lead to amputations of the lower extremities. The present therapy for the treatment of diabetic wounds mainly involves the use of synthetic moieties and other biotechnology-derived biomolecules, including growth factors. Few plant products are also useful in the treatment of wounds. METHODS: Essential oils derived from various herbs are reported to possess significant wound healing potential and promote blood clotting, help to fight infections, and accelerate the wound healing process. Hence, the present review is a systematic analysis of all the available data on the use of the natural oils with their biological source, active phytochemical constituents present, and the probable mechanism of action for the treatment of chronic and diabetic wounds in suitable animal models. A methodical collection of data was performed, and information was searched up to April 2020 in entirety. Key phrases used for the data search include the pathophysiology of wounds, diabetic foot wound and its complications, natural oils for chronic and diabetic wound treatment. RESULTS: This review summarizes the natural oils which are reported in the literature to be beneficial in the treatment of chronic wounds, while some oils have been specifically also studied against wounds in diabetic rats. Essential oils are said to interact with the body pharmacologically, physiologically and psychologically and help in rapid wound healing. However, the majority of the literature studies have demonstrated wound healing activity only in animal models (preclinical data), and further clinical studies are necessary. CONCLUSION: This review provides a platform for further studies on the effective utilization of natural oils in the treatment of chronic and diabetic wounds, especially if oils are to receive credibility in the management of chronic wounds.

In-silico Screening of Phytoconstituents on Wound Healing Targets - Approaches and Current Status.

Over recent years, there has been tremendous research focused on the effective utilization of natural products in wound management. Natural or herbal products contain several phytoconstituents that may act on various stages in wound healing and thereby provide a multi-targeted approach especially in the treatment of chronic wounds. Currently, attempts have been made to screen the phytoconstituents present in herbs on various targets involved in wound healing. This review includes a systematic evaluation of scientific reports by various groups of researchers on the herbals evaluated for wound management, their phytochemical profiling, pre-clinical studies, and molecular modeling studies. Various wound targets discussed include Interleukin-1, Interleukin-6, Tumor necrosis factor-α (TNF-α), Thymosin beta-4 (Tß-4) that regulate the early inflammatory stage and the novel T cell immune response cDNA 7(TIRC7) that regulates angiogenesis. Also, neuropeptides P and Y act on the inflammatory, migratory, and proliferation phases, and growth factors like vascular endothelial growth factor family (VEGF) and placental growth factor family (PGF) are involved in angiogenesis, while the role of Fibroblast growth factor in tissue remodeling is discussed. As many of the natural products include polyherbal systems, this approach can help in the judicious selection of a combination of herbs that will act on multiple targets in the wound healing process and provide a multi-factorial approach in wound management.

Evaluation of Glycemic Control and Predictors of Severe Illness and Death in Patients with Diabetes Hospitalized With COVID-19.

Objectives: To identify risk factors for severe disease and death among patients with diabetes and coronavirus disease 2019 (COVID-19) infection. Methods: This retrospective cohort study conducted at three hospitals included 733 consecutive patients with DM admitted with confirmed COVID-19 (March 1 - December 31, 2020). Multivariable logistic regression was performed to identify predictors of severe disease and death. Results: The mean age was 67.4 ± 14.3 years, 46.9% were males and 61.5% were African American. Among all patients, 116 (15.8%) died in the hospital. A total of 317 (43.2%) patients developed severe disease, 183 (25%) were admitted to an ICU and 118 (16.1%) required invasive mechanical ventilation. Increasing BMI (OR, 1.13; 95% CI, 1.02-1.25), history of chronic lung disease (OR, 1.49; 95% CI, 1.05-2.10) and increasing time since the last HbA1c test (OR, 1.25; 95% CI, 1.05-1.49) were the preadmission factors associated with increased odds of severe disease. Preadmission use of metformin (OR, 0.67; 95% CI, 0.47-0.95) or GLP-1 agonists (OR, 0.49; 95% CI, 0.27-0.87) was associated with decreased odds of severe disease. Increasing age (OR, 1.21; 95% CI, 1.09-1.34), co-existing chronic kidney disease greater than stage 3 (OR, 3.38; 95% CI, 1.67-6.84), ICU admission (OR, 2.93; 95% CI, 1.28-6.69) and use of invasive mechanical ventilation (OR, 8.67, 95% CI, 3.88-19.39) were independently associated with greater odds of in-hospital death. Conclusion: Several clinical characteristics were identified to be predictive of severe disease and in-hospital death among patients with underlying diabetes hospitalized with COVID-19.

Social Capital Theory, Social Exchange Theory, Social Cognitive Theory, Financial Literacy, and the Role of Knowledge Sharing as a Moderator in Enhancing Financial Well-Being: From Bibliometric Analysis to a Conceptual Framework Model.

A person's financial well-being (FWB) is the complete contentment gained from one's present financial condition. This has a powerful impact on the entire achievement of an employee's "well-being." Researchers, financial analysts, financial planners, educationists, and economists have explored the "enablers" to improve employees' living standards by investigating the possible "FWB" resources for decades. There is no literature available to show the connection between social capital theory, social exchange theory (SET), social cognitive theory (SCT), financial literacy and FWB, and employees' financial knowledge sharing a moderator to expand the complete FWB.

Herb-drug interactions in diabetes mellitus: A review based on pre-clinical and clinical data.

Global diabetes epidemic is the major cause of fatality and lethality. As per IDF 2019 report, diabetes caused 4.2 million deaths, approximately 463 million people are living with diabetes and by 2045, this will rise to 700 million. Nowadays, the physicians and common people in both developed and developing countries are using medicinal plants and their formulations to treat diseases with the postulation that organic commodities are safe for consumption. These plants may act as inhibitors or inducers of the Cytochrome P450 or transport and efflux proteins or both and may alter gastrointestinal, renal functions leading to Herb-Drug Interactions. This review intends to focus on the frequently employed medicinal plants, their traditional uses, their Cytochrome P450 inhibition or induction activity, phytochemical, and pharmacological effects, established HDI with the help of in vitro tools, in vivo pharmacokinetics and pharmacodynamics studies to understand the impact of herbs on ADME of the drug and whether it is beneficial, harmful or has no effect respectively. This review will help the physicians and other health care professionals as a reference guide to update their knowledge and expertise about HDI. However, more quality research in this area is needed to evaluate the efficacy of many herbal medicines, thereby reducing side effects and improving the safety of patients.

Prevalence and distribution of multilocus sequence types of Staphylococcus aureus isolated from bulk tank milk and cows with mastitis in Pennsylvania.

A total of 163 S. aureus isolates; 113 from mastitic milk (MM) and 50 from bulk tank milk (BTM) (2008, 2013-2015) submitted for bacteriologic analysis at the Penn State Animal Diagnostic Laboratory were examined for their phenotypic and genotypic characteristics. Multi-locus sequence typing (MLST) analysis identified 16 unique sequence types (STs) which belonged to eight clonal complexes (CCs). Majority of the isolates were variants of CC97 (68.7%) and CC151 (25.1%). CC97 comprised of seven STs, of which two were new STs (ST3273, ST3274), while CC151 comprised of three STs of which ST3272 was identified for the first time. Several farms had more than one ST type that were either members of the same clonal complex or unrelated STs. On one farm, six different STs of both categories were seen over the years within the farm. It was observed that ST352 and ST151 were the two main clonal populations in cattle not only in Pennsylvania but also globally. Most isolates were susceptible to all the antibiotics evaluated. 6.7% of isolates showed resistance to vancomycin and penicillin. Two isolates of ST398 showed multidrug resistance (>3 antibiotics) against clindamycin, erythromycin, tetracycline, and penicillin. It was noted that 59 of 163 (36.2%) isolates encoded for enterotoxigenic genes. Enterotoxin genes seg/sei accounted for ~85% of enterotoxin positive isolates. Toxic shock syndrome gene tsst-1 alone was positive in two isolates (ST352, ST 2187). 97.5% of CC151 isolates were enterotoxin seg/sei positive. Most isolates were positive for lukED (95%) and lukAB (96.3%) leukotoxin genes. Bovine specific bi-component leucocidin lukMF' was present in 54% of isolates. A prominent observation of this study was the explicit association of lukMF' with lineages ST151 and ST352. In conclusion, the findings of the study, suggest that small number of S. aureus STs types (ST352, ST2187, ST3028, and ST151) are associated with majority of cases of bovine mastitis in Pennsylvania dairy farms. It was observed that one ST of S. aureus predominated in the herd and this ST can coexist with several other ST types of S. aureus strains. When STs were interpreted along with virulence, leucocidin genes and antimicrobial resistance, ST-variants allowed better interpretation of the S. aureus molecular epidemiologic findings specifically for tracing recurrence or persistence of infections in cow over time, among cows in the herd, and between herds in Pennsylvania.

Novel Niacin Receptor Agonists: A Promising Strategy for the Treatment of Dyslipidemia.

BACKGROUND: Hyperlipidemia is characterized by high level of cholesterol and triglycerides in blood. Various classes of drugs like statins, fibrates, niacin etc. are used for treatment of hyperlipidaemia. OBJECTIVE: Niacin, which is one of the beneficial anti-hyperlipidemic agents, helps decreasing LDL cholesterol by 20 to 40% and causes increase of HDL cholesterol by 20 to 35%. However cutaneous flushing, loss of glucose tolerance, liver toxicity are the reported side effects of niacin therapy responsible for decreased patient compliance. Very recently, the G protein coupled receptor (GPCR); GPR109A located on the adipocytes has been identified as the receptor for activation of niacin. METHOD: In-vitro studies have demonstrated that GPR109A receptor having high affinity for niacin. The present review attempts to provide a systematic presentation of the various chemical classes of compounds that have been reported as novel niacin receptor agonists including pyrazole-3-carboxylic acids, urea derivatives, anthranilic acids, biaryl anthranilides, tetrahydro anthranilic acid, xanthines, barbituric acid, bicyclic pyrazole carboxylic acids, pyrido pyrimidinones, pyrazolyl propionyl cyclohexenamides, pyrazole acids etc. Results: As the design of GPR109A receptor agonists offers a promising solution for treatment of dyslipidemia, this review will be beneficial for medicinal and drug discovery chemists to expediate the process of discovery of new class of anti-hyperlipidemic agent with favorable lipid lowering profile with increase in HDL levels. CONCLUSION: This review explains novel GPR109A receptor agonists for the treatment of dyslipidemia.

Pharmacokinetics and Pharmacodynamic Herb-Drug Interaction of Piperine with Atorvastatin in Rats.

Herbals that are widely consumed as therapeutic alternatives to conventional drugs for cardiovascular diseases, may lead to herb-drug interactions (HDIs). Atorvastatin (ATR) is drug of choice for hyperlipidemia and is extensively metabolized through CYP3A4 enzyme. Thus, we postulate that concomitant administration of ATR with piperine (PIP, potent inhibitor of CYP3A4 enzyme)/ridayarishta (RID, cardiotonic herbal formulations containing PIP) may lead to potential HDI. A simple, accurate, sensitive high-performance liquid chromatography-photodiode array detection method using Kromasil-100 C18 column, mobile phase acetonitrile: 30 mM phosphate buffer (55:45 v/v) pH 4.5 with flow rate gradient programming was developed to study the potential HDI in rats. Method was found to be linear (2-100 ng/mL) with Lower Limit of Detection (LLOD) 2 ng/mL. The precision (%CV < 15%), accuracy (-1.0 to -10% R.E) with recoveries above 90% from rat plasma of ATR and IS were obtained. The pharmacokinetic (PK) interactions studies on co-administration of ATR (8.4 mg/kg, p.o.) with PIP (35 mg/kg, p.o.), demonstrated a threefold increase in Cmax of ATR (P < 0.01) with significant increase in AUC0-t/AUC0-∞ compared to ATR alone indicating potential PK-HDI. However co-administration of RID (4.2 mL/kg, p.o.) showed less significant changes (P > 0.05) indicating low HDI. The pharmacodynamic effects/interactions study (TritonX-100 induced hyperlipidemic model in rats) suggested no significant alterations in the lipid profile on co-administration of PIP/RID with ATR, indicating that there may be no significant pharmacodynamic interactions.

Reviving tourism industry post-COVID-19: A resilience-based framework.

The COVID-19 pandemic struck the tourism industry severely. Based on the review of 35 papers that studied the tourism industry in the wake of the pandemic, we propose a resilience-based framework for reviving the global tourism industry post-COVID-19. Our framework outlines four prominent factors for building resilience in the industry: government response, technology innovation, local belongingness, and consumer and employee confidence. We argue that using such inclusive resilience; the tourism industry may transform into a new global economic order characterized by sustainable tourism, society's well-being, climate action, and the involvement of local communities. We also offer directions for future research in the area.

Roles for a lipid phosphatase in the activation of its opposing lipid kinase.

Fig4 is a phosphoinositide phosphatase that converts PI3,5P2 to PI3P. Paradoxically, mutation of Fig4 results in lower PI3,5P2, indicating that Fig4 is also required for PI3,5P2 production. Fig4 promotes elevation of PI3,5P2, in part, through stabilization of a protein complex that includes its opposing lipid kinase, Fab1, and the scaffold protein Vac14. Here we show that multiple regions of Fig4 contribute to its roles in the elevation of PI3,5P2: its catalytic site, an N-terminal disease-related surface, and a C-terminal region. We show that mutation of the Fig4 catalytic site enhances the formation of the Fab1-Vac14-Fig4 complex, and reduces the ability to elevate PI3,5P2. This suggests that independent of its lipid phosphatase function, the active site plays a role in the Fab1-Vac14-Fig4 complex. We also show that the N-terminal disease-related surface contributes to the elevation of PI3,5P2 and promotes Fig4 association with Vac14 in a manner that requires the Fig4 C-terminus. We find that the Fig4 C-terminus alone interacts with Vac14 in vivo and retains some functions of full-length Fig4. Thus, a subset of Fig4 functions are independent of its phosphatase domain and at least three regions of Fig4 play roles in the function of the Fab1-Vac14-Fig4 complex.