Enzyme-Based Antiviral Potential of Cinnamomum verum J. Presl. Essential Oil and Its Major Component (E)-Cinnamaldehyde.

In the present study, Cinnamomum verum J. Presl. bark essential oil and its main component cinnamaldehyde was evaluated in vitro for neuraminidase (NA), transmembrane serine protease (TMPRSS2), and angiotensin converting enzyme 2 (ACE2) inhibitory activities. The chemical composition of C. verum essential oil was confirmed by both gas chromatography-mass spectrometry (GC/MS), and gas chromatography-flame ionization detection (GC-FID), where 75.9% (E)-cinnamaldehyde was the major component. The ACE2, NA, and TMPRSS2 enzyme inhibitions of C. verum bark essential oil at 20 µg/mL concentration, and (E)-cinnamaldehyde (5 µg/mL) were calculated and compared in the range of 54.2-89.9%. Molecular docking results supported that (E)-cinnam-aldehyde was specific to ACE2 with 89.9% inhibition. Our findings suggest further in vivo studies to confirm the effective and safe use of the essential oil as well as the (E)-cinnamaldehyde.

Association Between Venous Thromboembolism Prophylaxis and the Incidence of Thromboembolism Following Orthopedic Procedures: A Cross-Sectional Study.

INTRODUCTION: Venous thromboembolism (VTE) is a significant concern following orthopedic procedures, necessitating effective prophylactic measures. The rates of VTE prophylaxis, however, vary widely between institutions and nations, falling between 13% and 70% on average. In the absence of adequate thromboprophylaxis, pulmonary embolism, which accounts for 5% to 10% of mortality in hospitalized patients, is one of the leading causes of death. This study investigates the relationship between VTE prophylaxis and thromboembolism incidence, considering patient characteristics, risk assessment completion, anticoagulant prescription, and weight-bearing status. OBJECTIVES: To evaluate the knowledge gap by examining the relationship between VTE prevention and the prevalence of thromboembolism also to examine the anticoagulant prescription trends for patients being discharged from orthopedic operations and to investigate the connection between post-procedure weight-bearing status and the development of VTE problems. METHODOLOGY: A retrospective, cross-sectional design was employed, analyzing 200 orthopedic procedure patients from January to June of 2023 performed at Rehman Medical Institute. After getting ethical approval from the institutional ethical approval board, data were collected on the basis of variables encompassing patient attributes, surgery details, VTE risk factors, prophylaxis type, and VTE complications. Data was entered and analyzed via IBM SPSS Statistics for Windows, Version 22 (Released 2013; IBM Corp., Armonk, New York, United States), and the data were run through various tests including descriptive statistics, cross-tabulations, and chi-square. Results were then presented in the form of a table. RESULTS: Among 200 individuals 24 individuals experienced VTE, while 176 did not. Significant gender-based VTE differences were observed (p = 0.01). Hypertension (HTN) showed a significant association (p = 0.04) with VTE. Major surgeries were correlated with higher VTE incidence (p = 0.03). Pharmacological prophylaxis reduced the occurrence of VTE (p = 0.01). Early mobilization and Ted stockings were correlated with lower VTE incidence (p = 0.04, p = 0.12). CONCLUSION: This study reveals gender-specific VTE differences, emphasizes the role of HTN, surgical nature, and prophylaxis in VTE incidence, and supports tailored prophylactic strategies. Our findings align with previous research and emphasize the significance of tailored prophylaxis strategies. By examining multiple factors, including gender, co-morbidities, surgical characteristics, and prophylactic methods, our study contributes to the evidence base that supports clinical decision-making and enhances patient safety in orthopedic surgery.

Synthesis of Competitive and Noncompetitive Inhibitors of Alpha-Glucosidase and Anticancer Agents.

Imidazoles and phenylthiazoles are an important class of heterocycles that demonstrate a wide range of biological activities against various types of cancers, diabetes mellitus and pathogenic microorganisms. The heterocyclic structure having oxothiazolidine moiety is an important scaffold present in various drugs, with potential for enzyme inhibition. In an effort to discover new heterocyclic compounds, we synthesized 26 new 4,5-diphenyl-1H-imidazole, phenylthiazole, and oxothiazolidine heterocyclic analogues that demonstrated potent α-glucosidase inhibition and anticancer activities. Majority of the compounds noncompetitively inhibited α-glucosidase except for two that exhibited competitive inhibition of the enzyme. Docking results suggested that the noncompetitive inhibitors bind to an apparent allosteric site on the enzyme located in the vicinity of the active site. Additionally, the analogues also exhibited significant activity against various types of cancers including non-small lung cancer. Since tubulin protein plays an important role in the pathogenesis of non-small lung cancer, molecular docking with one of the target compounds provided important clues to its binding mode. The current work on imidazoles and phenylthiazole derivatives bears importance for designing of new antidiabetic and anticancer drugs.

Ternary Lithium Nickel Boride with 1D Rapid-Ion-Diffusion Channels as an Anode for Use in Lithium-Ion Batteries.

Anode materials with high-rate performances and good electrochemical stabilities are urgently required for the grid-scale application of lithium-ion batteries (LIBs). Theoretically, transition metal borides are desirable candidates because of their appropriate working potentials and good conductivities. However, the reported metal borides exhibit poor performances owing to their lack of favorable Li+ storage sites and poor structural stabilities during long-term charging/discharging. In this work, a ternary alkali metal boride, Li1.2 Ni2.5 B2 , which displays a high Li+ storage capacity and remarkable electrochemical stability and an excellent rate performance is studied. In contrast to conventional transition metal borides, the introduction of Li atoms facilitates the formation of 1D Ni/B-based honeycomb channels during synthesis. This Ni/B framework successfully sustains the strain during Li+ intercalation and deintercalation, and thus, the optimized Li1.2 Ni2.5 B2 anode exhibits an excellent cycle stability over 500 charge/discharge cycles. This electrode also exhibits superior reversible capacities of 350, 183, and 80 mA h g-1 at 0.1, 1, and 5 A g-1 , respectively, indicating the considerable potential of the 1D Ni/B framework as a commercially available fast-charging LIB anode.

Comparative In Vitro and In Silico Enzyme Inhibitory Screening of Rosa x damascena and Pelargonium graveolens Essential Oils and Geraniol.

The present work aims to evaluate Rosa x damascena Herrm. and Pelargonium graveolens L'Hér. essential oils, and the major constituent geraniol for their in vitro and in silico inhibitory activities against 5-lipoxygenase (5-LOX), cyclooxygenase (COX), acetyl cholinesterase (AChE), butyryl cholinesterase (BuChE), and angiotensin converting enzyme (ACE2) enzymes. Geraniol most potently inhibited the ACE2 relative to other enzymes. R. damascena essential oil moderately inhibited the cancer cell lines with no toxic effects on healthy HEK 293 cells. P. graveolens essential oil inhibited a number of cancer cell lines including A549, MCF7, PC3, and HEK 293 that are reported here for the first time. The molecular docking of geraniol with the target enzymes revealed that it binds to the active sites similar to that of known drugs. Geraniol carries the potential for further drug development due to its drug-like binding mode for the target enzymes. Our work confirms that these essential oils possess similar biological activities due to their similar phytochemistry in terms of the major constituents of the plants. The promising biological activities reported in this work further warrant the inclusion of in vivo studies to establish safe use of the target essential oils and their constituents.

Diffuse Coronary Artery Disease - A Challenge To Revascularize And The Role Of Coronary Endarterectomy.

Coronary endarterectomy is a useful adjunct procedure in patients with diffuse coronary artery disease when isolated coronary artery bypass grafting does not permit adequate revascularization. The primary aim of this procedure is to enable ample blood flow by removing the obstructing plaque. Herein we discuss the case of a middle-aged patient who underwent coronary endarterectomy.

Kinetic and isotherms modeling of methyl orange and chromium (VI) onto hexagonal ZnO microstructures as a membrane for environmental remediation of wastewater.

Globally, contamination of water by dyes and heavy metals (HMs) is a serious environmental and public health problem due to their carcinogenic and mutagenic nature. It is incumbent to treat innocuously before discharge. It is the first time, hexagonal zinc oxide (ZnO) microstructure are being employeed as a membrane in the simultaneous removal of methyl orange (MO) and chromium (Cr (VI)) from the aqueous solution. The surface chemistry of hexagonal ZnO was characterized for morphology, surface functional groups, crystalline nature, and elemental composition by scanning electron microscope (SEM), Fourier transmission infrared spectroscopy (FTIR), X-ray diffraction (XRD) and energy dispersive X-ray spectroscopy (EDX). Adsorption capacity and removal efficiency was determined by the laboratory batch adsorption experiments, while nonlinear, linear kinetics and isotherm models were fitted to experimental data to investigate the adsorption process. The results exhibited that the maximum adsorption capacity (qmax) of hexagonal ZnO from the Langmuir isotherm model was 80.39 mg g-1 and 84.10 mg g-1 for MO and Cr (VI) respectively. According to the modeling findings, linear langmuir fitted to the experimental data with R2 0.967 and 0.971 for both MO and Cr (VI) which indicates monolayer physical adsorption of both pollutants has taken place. Whereas, kinetic study showed nonlinear pseudo-second order with R2 0.989 and 0.986 for MO and Cr (VI) model best fitted with the experimental data. The values of thermodynamics parameters Gibbs free energy change ΔG°, heat of enthalpy ΔH° and, heat of entropy ΔS° indicate that spontaneous, endothermic, and irreversible adsorption reactions occurred. Overall, it is concluded from our observations that hexagonal ZnO has the potential to be used as an eco-friendly, cost-effective adsorbent for simultaneous remaoval of both MO and Cr (VI) from water. Findings of the current investigation provide valuable insights for the development of an inexpensive, effective and sustainable filtration method for the treatment of MO and Cr (VI) synergistically.

MXenes as Emerging Materials: Synthesis, Properties, and Applications.

Due to their unique layered microstructure, the presence of various functional groups at the surface, earth abundance, and attractive electrical, optical, and thermal properties, MXenes are considered promising candidates for the solution of energy- and environmental-related problems. It is seen that the energy conversion and storage capacity of MXenes can be enhanced by changing the material dimensions, chemical composition, structure, and surface chemistry. Hence, it is also essential to understand how one can easily improve the structure-property relationship from an applied point of view. In the current review, we reviewed the fabrication, properties, and potential applications of MXenes. In addition, various properties of MXenes such as structural, optical, electrical, thermal, chemical, and mechanical have been discussed. Furthermore, the potential applications of MXenes in the areas of photocatalysis, electrocatalysis, nitrogen fixation, gas sensing, cancer therapy, and supercapacitors have also been outlooked. Based on the reported works, it could easily be observed that the properties and applications of MXenes can be further enhanced by applying various modification and functionalization approaches. This review also emphasizes the recent developments and future perspectives of MXenes-based composite materials, which will greatly help scientists working in the fields of academia and material science.

Azole inhibitors of mushroom and human tyrosinases: Current advances and prospects of drug development for melanogenic dermatological disorders.

Azoles are a famous and promising class of drugs for treatment of a range of ailments especially fungal infections. A wide variety of azole derivatives are also known to exhibit tyrosinase inhibition, some of which possess promising activity with potential for treatment of dermatological disorders such as post-inflammatory hyperpigmentation, nevus, flecks, melasma, and melanoma. Recently, thiazolyl-resorcinol derivatives have demonstrated potent human tyrosinase inhibition with a safe and effective therapeutic profile for treatment of skin hyperpigmentation in humans, which are currently under clinical trials. If approved these derivatives would be the first azole drugs to be used for treatment of skin hyperpigmentation. Although the scientific literature has been witnessing general reviews on tyrosinase inhibitors to date, there is none that specifically and comprehensively discusses azole inhibitors of tyrosinase. Appreciating such potential of azoles, this focused review highlights a wide range of their derivatives with promising mushroom and human tyrosinase inhibitory activities and clinical potential for treatment of melanogenic dermatological disorders. Presently, these disorders have been treated with kojic acid, hydroquinone and other drugs, the design and development of which are based on their ability to inhibit mushroom tyrosinase. The active sites of mushroom and human tyrosinases carry structural differences which affect substrate or inhibitor binding. For this reason, kojic acid and other drugs pose efficacy and safety issues since they were originally developed using mushroom tyrosinase and have been clinically used on human tyrosinase. Design and development of tyrosinase inhibitors should be based on human tyrosinase, however, there are challenges in obtaining the human enzyme and understanding its structure and function. The review discusses these challenges that encompass structural and functional differences between mushroom and human tyrosinases and the manner in which they are inhibited. The review also gauges promising azole derivatives with potential for development of drugs against skin hyperpigmentation by analyzing and comparing their tyrosinase inhibitory activities against mushroom and human tyrosinases, computational data, and clinical profile where available. It aims to lay groundwork for development of new azole drugs for treatment of skin hyperpigmentation, melanoma, and related dermatological disorders.

Methods for Forming Human Lymphatic Microvessels In Vitro and Assessing their Drainage Function.

This chapter describes methods to engineer human lymphatic microvessels in vitro and to assess their fluid and solute drainage capacities. The lymphatics are formed within micropatterned type I collagen gels that contain a blind-ended channel for the growth of lymphatic endothelial cells. Because the vessels have one blind end and one open end each, they mimic the terminal structure of the native lymphatic microvascular tree. The solute drainage rates that are measured from the engineered lymphatics in vitro can be directly compared with published results from intact vessels in vivo. Practical considerations to increase the accuracy of the drainage assays are discussed.

Breast Tumor Detection and Classification in Mammogram Images Using Modified YOLOv5 Network.

Breast cancer incidence has been rising steadily during the past few decades. It is the second leading cause of death in women. If it is diagnosed early, there is a good possibility of recovery. Mammography is proven to be an excellent screening technique for breast tumor diagnosis, but its detection and classification in mammograms remain a significant challenge. Previous studies' major limitation is an increase in false positive ratio (FPR) and false negative ratio (FNR), as well as a drop in Matthews correlation coefficient (MCC) value. A model that can lower FPR and FNR while increasing MCC value is required. To overcome prior research limitations, a modified network of YOLOv5 is used in this study to detect and classify breast tumors. Our research is conducted using publicly available datasets Curated Breast Imaging Subset of DDSM (CBIS-DDSM). The first step is to perform preprocessing, which includes image enhancing techniques and the removal of pectoral muscles and labels. The dataset is then annotated, augmented, and divided into 60% for training, 30% for validation, and 10% for testing. The experiment is then performed using a batch size of 8, a learning rate of 0.01, a momentum of 0.843, and an epoch value of 300. To evaluate the performance of our proposed model, our proposed model is compared with YOLOv3 and faster RCNN. The results show that our proposed model performs better than YOLOv3 and faster RCNN with 96% mAP, 93.50% MCC value, 96.50% accuracy, 0.04 FPR, and 0.03 FNR value. The results show that our suggested model successfully identifies and classifies breast tumors while also overcoming previous research limitations by lowering the FPR and FNR and boosting the MCC value.

Incidence and Causes of Reintubation Other Than Reopening of the Chest in Post-Cardiac Surgical Patients in a Tertiary Care Hospital.

Objective To determine the incidence of endotracheal reintubation, excluding surgical reopening, in post-cardiac surgical patients in a tertiary care hospital. Material and methods A retrospective descriptive analysis of 408 patients who underwent different cardiac surgeries during this period. Post-operative extubation was performed when patients fulfilled the preset criteria for extubation, which include consciousness (awake and aware), stable vital signs, acceptable arterial blood gases, acceptable respiratory mechanics, a maximum inspiratory force greater than 20-25 cm H2O, chest tube drainage less than 100 ml per hour, normal temperature and electrolytes. The total number of patients who were reintubated within 72 hours of extubation was noted. The criteria for reintubation included altered conscious level with Glasgow Coma Score (GCS) of less than 8, respiratory failure, unstable hemodynamics, and arrhythmias such as ventricular tachycardia (VT) and fibrillation. All of the information was collected retrospectively on a specifically prepared form. Data was entered and evaluated in Statistical Package for the Social Sciences. The research was piloted in the Cardiac Intensive Care Unit (CICU) of Northwest General Hospital and Research Center, Hayatabad, Peshawar from December 2018 to March 2020. Results Out of 408 patients who had cardiac surgeries, only nine (2.2%) were reintubated after initial extubation. The average time for which patients remained on the ventilator was 8 ± 2 hours. The reasons for reintubation were recorded. Among those reintubated, eight patients (88.88%) had undergone coronary artery bypass grafting (CABG) whereas one patient (11.11%) had undergone mitral valve replacement (MVR). In three (33.33%) patients, stroke (hemiplegia in two and global brain ischemia in one) with low GCS was the primary cause of reintubation. Arrhythmias - which included VT, ventricular fibrillation (VF), and supraventricular tachyarrhythmias (SVT) - were responsible for three (33.33%) cases of reintubation. Respiratory failure - with a partial pressure of oxygen in arterial blood less than 60 mmHg, along with tachypnea - was responsible for reintubation in two (22.22%) patients. In one (11.11%) patient who had MVR, cardiac arrest was the underlying reason; the cause of arrest could not be retrieved from the retrospective data. Notably, as a common variable, five (62.5%) out of the eight reintubated CABG patients had a poor left ventricular function.  Conclusion Causes of reintubation were primarily cardiac (arrhythmias) and neurological, followed by respiratory causes in our center. Patients with poor left ventricular function and diffuse coronary artery disease appear to have a higher incidence of reintubation which can lead to extended CICU and hospital stay, elevated mortality, and higher costs.

Interstitial Hypertension Suppresses Escape of Human Breast Tumor Cells Via Convection of Interstitial Fluid.

INTRODUCTION: Interstitial hypertension, a rise in interstitial fluid pressure, is a common feature of many solid tumors as they progress to an invasive state. It is currently unclear whether this elevated pressure alters the probability that tumor cells eventually escape into a neighboring blood or lymphatic vessel. METHODS: In this study, we analyze the escape of MDA-MB-231 human breast tumor cells from a ~3-mm-long preformed aggregate into a 120-µm-diameter empty cavity in a micromolded type I collagen gel. The "micro-tumors" were located within ~300 µm of one or two cavities. Pressures of ~0.65 cm H2O were applied only to the tumor ("interstitial hypertension") or to its adjacent cavity. RESULTS: This work shows that interstitial hypertension suppresses escape into the adjacent cavity, but not because tumor cells respond directly to the pressure profile. Instead, hypertension alters the chemical microenvironment at the tumor margin to one that hampers escape. Administration of tumor interstitial fluid phenocopies the effects of hypertension. CONCLUSIONS: This work uncovers a link between tumor pressure, interstitial flow, and tumor cell escape in MDA-MB-231 cells, and suggests that interstitial hypertension serves to hinder further progression to metastatic escape. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12195-020-00661-w) contains supplementary material, which is available to authorized users.

Humanin: A mitochondrial-derived peptide in the treatment of apoptosis-related diseases.

Humanin (HN) is a small mitochondrial-derived cytoprotective polypeptide encoded by mtDNA. HN exhibits protective effects in several cell types, including leukocytes, germ cells, neurons, tissues against cellular stress conditions and apoptosis through regulating various signaling mechanisms, such as JAK/STAT pathway and interaction of BCL-2 family of protein. HN is an essential cytoprotective peptide in the human body that regulates mitochondrial functions under stress conditions. The present review aims to evaluate HN peptide's antiapoptotic activities as a potential therapeutic target in the treatment of cancer, diabetes mellitus, male infertility, bone-related diseases, cardiac diseases, and brain diseases. Based on in vitro and in vivo studies, HN significantly suppressed the apoptosis during the treatment of bone osteoporosis, cardiovascular diseases, diabetes mellitus, and neurodegenerative diseases. According to accumulated data, it is concluded that HN exerts the proapoptotic activity of TNF-α in cancer, which makes HN as a novel therapeutic agent in the treatment of cancer and suggested that along with HN, the development of another mitochondrial-derived peptide could be a viable therapeutic option against different oxidative stress and apoptosis-related diseases.

Matrix Pore Size Governs Escape of Human Breast Cancer Cells from a Microtumor to an Empty Cavity.

How the extracellular matrix (ECM) affects the progression of a localized tumor to invasion of the ECM and eventually to vascular dissemination remains unclear. Although many studies have examined the role of the ECM in early stages of tumor progression, few have considered the subsequent stages that culminate in intravasation. In the current study, we have developed a three-dimensional (3D) microfluidic culture system that captures the entire process of invasion from an engineered human micro-tumor of MDA-MB-231 breast cancer cells through a type I collagen matrix and escape into a lymphatic-like cavity. By varying the physical properties of the collagen, we have found that MDA-MB-231 tumor cells invade and escape faster in lower-density ECM. These effects are mediated by the ECM pore size, rather than by the elastic modulus or interstitial flow speed. Our results underscore the importance of ECM structure in the vascular escape of human breast cancer cells.

Role of Intraoperative Nerve Monitoring During Parathyroidectomy to Prevent Recurrent Laryngeal Nerve Injury.

Injury to the recurrent laryngeal nerve (RLN) is a well known, though less frequent, complication of parathyroid surgery. In recent years, the use of intraoperative nerve monitoring (IONM) has gained popularity amongst surgeons when operating on thyroid gland; however, its utilization in parathyroid surgery is not established. This trend continues to rise, despite multiple studies documenting no statistically significant difference that IONM decreases the incidence of RLN injury. Most surgeons use this technology as an adjunct to visualization alone for identification of RLN. The purpose of this review is to discuss the possible role of IONM in parathyroid surgery with regards to the accuracy, efficacy, and recent trends in the utilization of this technology. There is insufficient evidence that IONM reduces the risk of RLN injury in parathyroidectomy. Although IONM may decrease the likelihood of nerve injury by helping to identify and map the RLN during thyroidectomy, we did not find studies exclusive to parathyroid surgery to see if its use can be supported for parathyroidectomy. Despite this lack of evidence, we believe that IONM is a promising adjunct to visualization alone in detecting nerve structures during neck dissection, but more clinical trials are warranted to establish its role in preventing nerve injury in parathyroid surgery.

New potent inhibitors of tyrosinase: novel clues to binding of 1,3,4-thiadiazole-2(3H)-thiones, 1,3,4-oxadiazole-2(3H)-thiones, 4-amino-1,2,4-triazole-5(4H)-thiones, and substituted hydrazides to the dicopper active site.

A series of 1,3,4-thiadiazole-2(3H)-thiones, 1,3,4-oxadiazole-2(3H)-thiones, 4-amino-1,2,4-triazole-5(4H)-thiones, and substituted hydrazides were tailored and synthesized as new potent inhibitors of tyrosinase. The rationale for inhibitor design was based on the active site structural evidence from the crystal structures of bacterial tyrosinase and potato catechol oxidase enzymes. Kinetic and active site binding studies suggested mono-dentate binding of thiadiazole, oxadiazole, and triazole rings to the active site dicopper center of tyrosinase including hydrophobicity contributing to the potent inhibition. Kinetic plots showed mixed-type of inhibition by all 25 compounds. Substitutions at C3 of the triazole ring and C5 of the thiadiazole/oxadiazole rings were found to be playing a major role in the high binding affinity to tyrosinase. The current work may help develop new potent tyrosinase inhibitors against hyperpigmentation including potential insecticides.