Search

Internet of Medical Things (IoMT) can be leveraged for periodic sensing and recording of different health parameters using sensors, wireless communications, and computation platforms. Health care systems can be enhanced by using IoMT for remote patient monitoring and data-driven diagnosis powered by machine learning algorithms. In the context of IoMT, federated learning (FL) is an excellent choice to manage machine learning (ML) algorithms to drive this analysis. This is because FL models can be trained in a distributed manner on local heterogeneous datasets that all contribute to the "collective wisdom". The model parameters can be regulated and shared without sharing the actual health data, ensuring confidentiality and security. This paper makes a case for the viability of FL-based analysis of data acquired via IoMT by presenting some use cases and recent work in this area and proposing a novel framework for data analysis using FL specifically in the context of mental stress detection. It shows that FL-based methods can significantly reduce the required communication overhead for each local device from 10.02MB/day up to only 754B/day as compared to non-FL techniques. [ABSTRACT FROM AUTHOR]

The process of developing of new drugs is greatly hampered by their inadequate physicochemical, pharmacokinetic, and intrinsic characteristics. In this regard, the selected chloro indolinone, (Z)-6-chloro-3-(2-chlorobenzylidene)indolin-2- one (C1), and nitro indolinone, (Z)-6-chloro-3-(2-nitrobenzylidene)indolin-2- one (C2), were subjected to SwissADME and density function theory (DFT) analysis. For compounds C1 and C2, the BOILED-Egg pharmacokinetic model predicted intestinal absorption, blood-brain barrier (BBB) penetration, and p-glycoprotein interaction. According to the physicochemical analysis, C1 has exceptional drug-like characteristics suitable for oral absorption. Despite only being substrates for some of the major CYP 450 isoforms, compounds C1 and C2 were anticipated to have strong plasma protein binding and efficient distribution and block these isoforms. The DFT study using the B3LYP/6-311G(d,p) approach with implicit water effects was performed to assess the structural features, electronic properties, and global reactivity parameters (GRP) of C1 and C2. The DFT results provided further support for other studies, implying that C2 is more water-soluble than C1 and that both compounds can form hydrogen bonds and (weak) dispersion interactions with other molecules, such as solvents and biomolecules. Furthermore, the GRP study suggested that C1 should be more stable and less reactive than C2. A concentration-dependent 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'- azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging activity was shown by both C1 and C2. In brief, this finding has provided a strong foundation to explore furtherthe therapeutic potential of these molecules against a variety of human disorders. [ABSTRACT FROM AUTHOR]

The compounds were synthesized by refluxing 6-chlorooxindole with 2,3-dichlorobenzaldehyde and 2,6-dichlorobenzaldehyde in the presence of piperidine as a catalyst and characterized by spectroscopic analysis using 1H NMR, 13C NMR, and mass spectrometry as (E)-3-(2,3-dichlorobenzylidene)-6-chloroindolin-2-one (C-1) and (E)-3-(2,6-dichlorobenzylidene)-6-chloroindolin-2-one (C-2). Additionally, in silico ADME studies indicated that C-1 and C-2 with 1,1 rotatable bonds could have moderate water solubility and therefore could have the potential ability to cross the blood-brain barrier. Both showed high GI absorption, indicating that they are suitable for intestinal absorption while the compounds showed CYP1A2, CYP2C19, and CYP2C9 inhibition. The five drug-likeness criteria, which were Lipinski, Muegge, Ghose, Veber, and Egan, and the principles of drug-likeness are not violated by compounds C-1 and C-2. Also, the DFT computations were performed at the B3LYP level and at 6-311++G ∗ ∗ basis set to evaluate and support the obtained results from the experiment. The FMO results revealed that C-1 could likely prefer the intramolecular interactions rather than the intermolecular interactions, and vice versa for C-2. In addition, the NBO results indicated that the resonance interaction, especially the shift of electron to empty orbitals from lone pair electrons of nitrogen, would contribute to the stabilization of both compounds greatly. In DPPH assay, the compounds showed IC50 values of 37.390 and 34.676 μM, respectively. Similarly, in ABTS assay, the calculated IC50 values for the compounds were 25.381 and 33.706 μM, respectively. In short, these results provided a solid ground for further preclinical studies in quest of new effective therapeutic agents. [ABSTRACT FROM AUTHOR]

In this paper, the existence of a unique solution is established for a coupled system of Langevin fractional problems of ψ -Caputo fractional derivatives with generalized slit-strip-type integral boundary conditions and impulses using the Banach contraction principle. We also find at least one solution to the aforementioned system using some assumptions and Schaefer's fixed point theorem. After that, Ulam–Hyers stability is discussed. Finally, to provide additional support for the main results, pertinent examples are presented. [ABSTRACT FROM AUTHOR]

Gait and balance are an intricate interplay between the brain, nervous system, sensory organs, and musculoskeletal system. They are greatly influenced by the type of footwear, walking patterns, and surface. This exploratory study examines the effects of the Infinity Walk, pronation, and footwear conditions on brain effective connectivity patterns. A continuous-wave functional near-infrared spectroscopy device collected data from five healthy participants. A highly computationally efficient connectivity model based on the Grange causal relationship between the channels was applied to data to find the effective relationship between inter- and intra-hemispheric brain connectivity. Brain regions of interest (ROI) were less connected during the barefoot condition than during other complex walks. Conversely, the highest interconnectedness between ROI was observed while wearing flat insoles and medially wedged sandals, which is a relatively difficult type of footwear to walk in. No statistically significant (p-value < 0.05 ) effect on connectivity patterns was observed during the corrected pronated posture. The regions designated as motoric, sensorimotor, and temporal became increasingly connected with difficult walking patterns and footwear conditions. The Infinity Walk causes effective bidirectional connections between ROI across all conditions and both hemispheres. Due to its repetitive pattern, the Infinity Walk is a good test method, particularly for neuro-rehabilitation and motoric learning experiments. [ABSTRACT FROM AUTHOR]

In urban architecture, the lives and belongings of people begin to cause enormous casualties. An automatic fire alarm system is used to detect the fire in the house. This paper explores the framework for automatic fire warning, composition, and functioning. The fire warning system is a mix of several systems that work together to identify and alert people when smoke is a fire utilizing visual and auditory devices. Smoke sensors or heat sensors may trigger the alarm used in the fire alarm system. Alarms may either be engine bells or sounders or horns mountable on a wall. In keeping and controlling secure conditions and situations of all kinds, the fire alarm system plays a major role. However, it is understood that many modern fire alarms and detection systems can be operated at high costs. The device is collected by the fire alert sensor for fire, failure, and other signals that are sent to the submachine, The re-transmission of such data will be sent to the fire alarm control and then the controller, sound, and light alarm monitor, alarm and other equipment will start. The main aim of this Fire Alarm Management System is to create a fire control and deletion system with cost reliability in building automation using PLC. The BASS fire alarm control system has three major systems: (1) fire warning, (2) alarm and control, and (3) the equipment to open the door and the lift to the ground for security purposes. The fire detector is the warning machine. This machine has elements, such as a flame sensor, a smoke detector, and a heat detector, including bimetallic strips. The key aim of the analysis was the assembly of a PLC-based fire alarm system with a programmable logic controller and its output in the field of smoke and heat detection and its effect on the automatic alarm and sprinkling (PLC). For control and extinguishing of fires, this device is the most powerful. [ABSTRACT FROM AUTHOR]

Various derivatives of thiazolidine-2,4-dione (C1–C5) were designed and synthesized by chemical reaction with 4-nitrobenzaldehyde using Knoevenagel reaction conditions which results in the reduction of nitro group to amine and further modification results in target compounds. The chemical structures of all the 2,4-thiazolidinedione derivatives have been elucidated by 1H and 13C NMR spectroscopy. These compounds were further characterized by in silico ADME (absorption, distribution, metabolism, and excretion) studies. The pharmacokinetic properties were assessed by SwissADME software. The in silico ADME (absorption, distribution, metabolism, and excretion) assessment reveals that all derivatives (C1 to C5) have 5 to 7 rotatable bonds. Lipophilicity and water solubility showed that C1, C2, and C4 are water soluble except for C3 and C5 which are moderately soluble. All the compounds have high GI absorption except C3. None of the derivatives are blood-brain barrier permeant. Drug metabolism of TZDs derivatives showed that C3 was identified as an inhibitor of CYP2C9 and C5 as an inhibitor of CYP1A2 and CYP2C19. Drug likeness properties indicate that C1 has only one violation of the Ghose rule while C3 has violations in the Ghose and Egan rules. The in silico pharmacokinetic studies revealed high GI absorption and the inability to pass blood-brain barrier which can be further assessed by in vitro and in vivo antihyperglycemic activity. This study will contribute to providing TZDs derivatives with an improved pharmacokinetic profile and decreased toxicity. [ABSTRACT FROM AUTHOR]

The purpose of this study is to investigate the exchange reaction taking place among the bovine serum albumin (BSA), 5,5 ′ -dithiobis-(2-nitrobenzoic acid (ESSE), reduced glutathione, N-acetylcysteine, D-penicillamine (thiolates), and silver metal (AgI). For this purpose, stock solutions of BSA and Ellman's reagent were prepared by dissolving 264 mg of BSA in 5 ml of reaction buffer (0.1 M KH2PO4 at pH 7.8) and 23.8 mg of ESSE in 1.0 ml of reaction buffer which were mixed together. Mixture of BSA-AgI was prepared in a separate procedure by dissolving 0.17 mg of silver nitrate in 1 ml of reaction buffer and then dissolving BSA (200 mg) in the same solution of silver nitrate. Blocking of Cys-34 of BSA with AgI was confirmed by treating different dilutions of BSA-AgI (500 μM) solutions with the solutions of ESSE (85 μM) and ES- (85 μM) and recording the spectra (300-450) with a UV-visible spectrophotometer. The chromatographed AgI-modified BSA ((BSA-S)AgI)) samples (typically 500 μM) were subsequently mixed with thiolates (reduced glutathione, N-acetylcysteine, and D-penicillamine). AgI and modified BSA (typically 500 μM each) were treated with these low molecular weight thiolates and allowed to react overnight followed by chromatographic separation (Sephadex G25). The redox reactions of AgI-modified BSA with various low molecular weight thiols revealed a mechanically important phenomenon. In the case of reduced glutathione and N-acetylcysteine, we observed the rapid release of a commensurate amount of Ellman's anion, indicating that an exchange has taken place and low molecular weight thiols (RSH) substituted AgI species at the Cys-34 of BSA eventually forming disulfide (BSA-SSR) at Cys-34. It can be anticipated from the phase of study involving bovine serum albumin that low molecular weight thiolates (reduced glutathione and N-acetylcysteine) take off AgI which are attached to proteins elsewhere in the physiological system, making these toxic metals free for toxic action. [ABSTRACT FROM AUTHOR]

Kaempferol is a natural flavonoid, which has been widely investigated in the treatment of cancer, cardiovascular diseases, metabolic complications, and neurological disorders. Nrf2 (nuclear factor erythroid 2-related factor 2) is a transcription factor involved in mediating carcinogenesis and other ailments, playing an important role in regulating oxidative stress. The activation of Nrf2 results in the expression of proteins and cytoprotective enzymes, which provide cellular protection against reactive oxygen species. Phytochemicals, either alone or in combination, have been used to modulate Nrf2 in cancer and other ailments. Among them, kaempferol has been recently explored for its anti-cancer and other anti-disease therapeutic efficacy, targeting Nrf2 modulation. In combating cancer, diabetic complications, metabolic disorders, and neurological disorders, kaempferol has been shown to regulate Nrf2 and reduce redox homeostasis. In this context, this review article highlights the current status of the therapeutic potential of kaempferol by targeting Nrf2 modulation in cancer, diabetic complications, neurological disorders, and cardiovascular disorders. In addition, we provide future perspectives on kaempferol targeting Nrf2 modulation as a potential therapeutic approach. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is a multifactorial chronic metabolic disorder, characterized by altered metabolism of macro-nutrients, such as fats, proteins, and carbohydrates. Diabetic retinopathy, diabetic cardiomyopathy, diabetic encephalopathy, diabetic periodontitis, and diabetic nephropathy are the prominent complications of diabetes. Inflammatory mediators are primarily responsible for these complications. Curcumin, a polyphenol derived from turmeric, is well known for its anti-oxidant, anti-inflammatory, and anti-apoptotic properties. The regulation of several signaling pathways effectively targets inflammatory mediators in diabetes. Curcumin's anti-inflammatory and anti-oxidative activities against a wide range of molecular targets have been shown to have therapeutic potential for a variety of chronic inflammatory disorders, including diabetes. Curcumin's biological examination has shown that it is a powerful anti-oxidant that stops cells from growing by releasing active free thiol groups at the target location. Curcumin is a powerful anti-inflammatory agent that targets inflammatory mediators in diabetes, and its resistant form leads to better therapeutic outcomes in diabetes complications. Moreover, Curcumin is an anti-oxidant and NF-B inhibitor that may be useful in treating diabetes. Curcumin has been shown to inhibit diabetes-related enzymes, such as a-glucosidase, aldose reductase and aldose reductase inhibitors. Through its anti-oxidant and anti-inflammatory effects, and its suppression of vascular endothelial development and nuclear transcription factors, curcumin has the ability to prevent, or reduce, the course of diabetic retinopathy. Curcumin improves insulin sensitivity by suppressing phosphorylation of ERK/JNK in HG-induced insulin-resistant cells and strengthening the PI3K-AKT-GSK3B signaling pathway. In the present article, we aimed to discuss the anti-inflammatory mechanisms of curcumin in diabetes regulated by various molecular signaling pathways. [ABSTRACT FROM AUTHOR]

In this study, the anti-nociceptive potential of Schiff bases derivatives of 4-aminoantioyrine, (Z)-4-(4-hydroxy-3-methoxybenzylideneamino)-2, 3-dimethyl-1-phenyl-1, 2dihydropyrazol-5-one 1 and (Z)-4-(2-nitrobenzylideneamino)-2, 3-dimethyl-1-phenyl-1-2-dihydropyrazol-5-one 2 were tested in various mice pain models and their binding affinities with different drug targets were evaluated through molecular docking studies. The binding scores were calculated through molecular docking techniques for receptor sensitivity. Acute toxicity test suggests the safety of both compounds up 200 mg/kg. In the righting test, compound 1 and 2 had a significant effect in a dose-dependent manner and showed 59.46% and 48.40% blockade of pain at 150 mg/kg, respectively. In the formalin test, dose-dependently compound 1 showed 52.95% and 62.02% of inhibition in the early and late phase at 150 mg/kg. Similarly, Compound 2 showed 45.74% and 55.95% inhibition in the early and late phases at 150 mg/kg, respectively. In the tail immersion test, both compounds caused significant pain inhibition during various assessment times with maximum effects at 74.94% and 66.80% for 1 and 2 respectively at 150 mg/kg after 120 min. In molecular docking studies, compounds 1 and 2 showed a greater affinity for LOX with a docking score of –6.50 and 6.57 respectively. Similarly, for compounds 1 and 2 the docking was –4.94 and –4.83 with COX-1 while –5.10 and –4.85 with COX-2, respectively. Taken together, both the compounds exhibited marked antinociceptive effects in various pain-induced models possibly mediated by inhibition of LOX and COX pathways. [ABSTRACT FROM AUTHOR]

The complex conductivity dependent absorption, dispersion, refractive index, phase velocity and Fizeau's light dragging coefficients are investigated in this article. The refractive index linearly enhances with the amplitude of complex conductivity. The value of refractive index is enhanced from 1.35 to 15 as amplitude of complex conductivity | σ | varies from 20 S / m to 5000 S / m. The phase velocity has an inverse relation with the refractive index n r. The value of phase velocity decreases from 3 × 1 0 8 m/s to 2 × 1 0 7 m/s as | σ | varies from 20 S / m to 5000 S / m. A large Fizeau's dragging coefficient is observed at conductivity phase ϕ c = π. It is investigated that the Fizeau's dragging coefficient increases or decreases exponentially as a function of control fields Rabi frequencies. The phase shift give peaks at different values of probe detuning and slowly decreases with increasing the amplitude of complex conductivity. • Optical properties vary with complex conductivity, affecting absorption and dispersion. • Absorption and dispersion depend on probe detuning and control field Rabi frequencies. • Increased control field strength splits the absorption peak and reduces resonance absorption. • Refractive index changes with dispersion regions and complex conductivity values. • Phase velocity decreases with higher complex conductivity, showing sensitivity. [ABSTRACT FROM AUTHOR]

Metallo-elements have both pharmacological and toxic effects on plants, animals and humans. These are considered as a major public health issue worldwide. In particular, heavy metals such as silver (Ag) and aluminum (Al) are environmentally widespread, and their relative toxicity can lead to numerous pathologies such as nephropathy, cancers, vascular and skin diseases. The goal of this study was to examine the behavioral effects of Ag and Al salts (i.e. Silver nitrate and Aluminum sulfate) on glutathione (GSH), a potent oxidant in biological mixtures. We also aimed to suggest mechanisms of action of thiolate complexed to these metallo-elements in competitive studies with Ellman's reagent (5,5'-dithiobis(2-nitrobenzoic acid aka ESSE). By proton nuclear magnetic resonance (NMR) spectroscopy, detailed titrations were carried out for these metal thiols interactions in the presence of ESSE in order to elucidate first equilibrium and possible second equilibrium. We found by 1H NMR spectroscopy that GSH binds to Ag and Al, which highlighted possible in-vivo chelation mechanisms of GSH toward these toxic metallo-elements. [ABSTRACT FROM AUTHOR]

Membraneless microfluidic enzymatic biofuel cells (μEBFCs) operated under the co-laminar flow of fuel and oxidant often face cross-mixing issues, especially at low flow rates. In this work, we propose a new approach to design the single-stream μEBFC based on the investigation of relative positions of the electrodes at the top and bottom of the microchannel. To achieve this, a μEBFC was fabricated with multiwalled carbon nanotube (MWCNT) electrodes via a stencil method. The bioanode and biocathode were modified with glucose dehydrogenase and laccase via direct covalent bonding, respectively. The best results were attained by placing the cathode at the top and anode at the bottom of the microchannel in a Y-shaped two streamflow μEBFC. When a single electrolyte stream was used to achieve more practicality and ease of use, the performance was reduced by 40%. However, with the new design of electrodes in single-stream μEBFC, i.e. cathode at the top and anode at the bottom facing each other in the microchannel, the performance was recovered by 20%. This corresponds to maximum current and power density of 216 ± 12 μA cm−2 and 69.2 ± 9.2 μW cm−2, respectively. The stacking ability of the device was realized by connecting the two cells in series and parallel. The maximum power density delivered by the two single-stream μEBFCs' stack reached 160 μW cm−2 at 0.3 V. Thus, this study validates the viability of using single-stream μEBFCs in large stacks to power microelectronics more simply and practically. • The effect of electrode positions in microfluidic enzymatic biofuel cell (μEBFC) is studied. • The performance is improved by placing the cathode at the top of the microchannel. • A simplified single-stream device is designed to achieve more practicality. • With the new design of electrodes, the performance is enhanced by 20%. • Such a device demonstrates viability to easily stack in large numbers to produce the targeted power. [ABSTRACT FROM AUTHOR]

Punarnavine (PN) has been isolated from the roots of Boerhaavia diffusa L. (Nyctaginaceae). It is an important medicinal plant with a vast historical ethnopharmacological background. Its identification resulted from the interrogation of 'Punarnava', a tribal medicinal product. The molecule exhibited its position as incipient anticancer therapeutic agent. The inhibition of NFκB, ATF-2, c-Fos, and CREB-1 are one of the underlying mechanisms of anticancer action along with modification of the immune system. These signalling molecules are upregulated in the cancer microenvironment. Punarnavine also modified the release of interleukins, i.e., upregulated IL-2, IL-7, IL-10, IL-12, IFN-γ, while downregulated IL-1β, IL-6, TNF-α, VEGF, and GM-CSF. Punarnavine has exhibited its anticancer potential in murine melanoma cell lines, breast cancer and its metastasis to lungs, liver, and lymph nodes by modifying apoptotic pathways and even suppressing metastatic genes like TIMP-1, TIMP-2, MMP-2, MMP-9 and VEGF. The pharmacokinetic and basic drug discovery properties are also discussed concerning in silico databases. This approach exhibited PN as a successful molecule for drug development. The drug-likeness, solubility, GIT absorption, drug metabolism, and bioavailability of PN are promising of its drug candidature and therefore need further detailed studies to ascertain its clinical potential. This article is a preview of the preclinical anticancer profile of Punarnavine, including the computational approach of its drug-like properties. [ABSTRACT FROM AUTHOR]

In current work, silver nanoparticles (AgNPs) were prepared by a rapid biogenic technique "Green method" utilizing root extract of Olea ferruginea. The synthesized nanoparticles were characterized for UV visible spectroscopy, Fourier Transform Infrared Spectroscopy (FTIR), X-ray Diffraction (XRD), Scanning electron microscopy (SEM), High Resolution Transmission Electron Microscopy Studies (HRTEM) and biological assays. UV visible absorption spectroscopy confirms the formation of AgNPs by giving Surface Plasmon Resonance (SPR) peak at 430 nm. FTIR study showed occurrence of various functional groups present in root extract of Olea ferruginea. X-ray diffraction analysis determined the crystalline nature of bio-fabricated silver nanoparticles. The elemental composition of green made silver nanoparticles was studied through Energy Dispersive Spectroscopy (EDS) analysis. SEM & HRTEM study revealed the size, shape, surface morphology & dispersion level of molecules. The biologically synthesized AgNPs showed high antimicrobial, antifungal and antioxidant activity. The AgNPs are observed to be an excellent catalyst on reduction of hazardous dyes, which is confirmed by a decrease in absorbance of maximum values. [ABSTRACT FROM AUTHOR]

Objective: To compare our experience of genitourinary injuries during the war against terrorism with the record of those in previous wars of the World. Study Design: Cross sectional study. Place and Duration of Study: Urology department, Combined Military Hospital Peshawar, from Jun 2011 to Aug 2014. Methodology: We treated 89 (5.6%) cases of genitourinary injuries received in our tertiary care hospital in Khyber Pakhtunkhwa. The hospital was located at a distance of 2-3 hours of evacuation time by helicopter from the forward operational area. Results: The frequency of genitourinary injuries among 1589 war casualties was (5.6%). Out of these 49 (55%) were due to sniper shots and 40 (45%) due to improvised explosive device. Kidney was the most common organ injured 30 (33.7%), followed by bladder 20 (22.5%) and urethra 14 (15.7%). Majority of renal and bladder injuries were afflicted in those soldiers who were not wearing the protective jackets. Associated injuries to other organs were identified in 81% cases. Salvage of all genitourinary organs was the aim; however, nephrectomy and orchiectomy had to be performed in 30% and 50% respectively. Conclusion: Salvage of genitourinary war injuries poses a challenge to the trauma surgeon as lifesaving measures take precedence over organ preservation. Renal trauma in war was found to be the leading critical genitourinary injury. [ABSTRACT FROM AUTHOR]

Background: MicroRNAs (miRNAs) are small RNA molecules that modulate post-transcriptional gene regulation. They are often used as promising non-invasive biomarkers for the early diagnosis of cancer. However, their roles in assisted reproduction are still unknown. Methods: This prospective study was designed to evaluate the expression profiles of seven extracellular miRNAs (miR-7-5p, miR-202-5p, miR-378-3p, miR-224, miR-320a, miR-212-3p, and miR-21-5p) in human follicular fluid (FF) to explore the outcomes of in vitro fertilization (IVF). Of 255 women, 145 were without polycystic ovary syndrome (PCOS), and their ovarian assets were normal (NOR), while 110 were with normo-androgenic PCOS. Results: The combination of six FF miRNAs expression profile discriminated between PCOS and NOR women with a sensitivity of 79.2% and a specificity of 87.32% (AUC = 0.881 [0.61; 0.92], p = 0.001). MiR-202-5p significantly had a lower abundance level, and miR-378-3p had a high abundance level in pooled FF samples from patients treated with human menopausal gonadotropin (hMG) than those treated with recombinant follicle-stimulating hormone (rFSH) (p < 0.001). Our results showed that miRNA-320a was significantly different in top-quality embryos versus non-top-quality embryos on day 3 in NOR patients with a sensitivity of 80% and specificity of 71%, (AUC = [0.753 (0.651; 0.855)], p = 0.001). For clinical pregnancy outcome prediction, FF miRNA-21 exhibited high sensitivity (74.8%) and specificity (83.7%) with the AUC value of 0.774 (0.682; 0.865). Conclusion: Conclusively, our results provide evidence that miR-7-5p, miR-378-3p, miR-224, miR-212-3p were a differentially high expression in normo-androgenic PCOS patients than NOR patients. While miRNA-320a was significantly different in top-quality embryos versus non-top-quality embryos on day 3 (p = 0.001). The expression level of FF miR-212-3p was significantly related to the probability of embryos to develop into a high-quality blastocyst in patients with normal ovarian reserve. [ABSTRACT FROM AUTHOR]

Irrespective of sex and age, cancer is the leading cause of mortality around the globe. Therapeutic incompliance, unwanted effects, and economic burdens imparted by cancer treatments, are primary health challenges. The heritable features in gene expression that are propagated through cell division and contribute to cellular identity without a change in DNA sequence are considered epigenetic characteristics and agents that could interfere with these features and are regarded as potential therapeutic targets. The genetic modification accounts for the recurrence and uncontrolled changes in the physiology of cancer cells. This review focuses on plant-derived flavonoids as a therapeutic tool for cancer, attributed to their ability for epigenetic regulation of cancer pathogenesis. The epigenetic mechanisms of various classes of flavonoids including flavonols, flavones, isoflavones, flavanones, flavan-3-ols, and anthocyanidins, such as cyanidin, delphinidin, and pelargonidin, are discussed. The outstanding results of preclinical studies encourage researchers to design several clinical trials on various flavonoids to ascertain their clinical strength in the treatment of different cancers. The results of such studies will define the clinical fate of these agents in future. [ABSTRACT FROM AUTHOR]

Phellinus linteus is a valuable edible and medicinal mushroom. Since the early 1990s, it has drawn significant attention from consumers due to its potential functional and medicinal benefits. P. linteus and its bioactive compounds have demonstrated various biological activities, such as antioxidant, anti-inflammatory, anticancer, and hepatoprotective agents. This review systematically summarized the anticancer effects of the edible and medicinal mushroom, P. linteus, and its molecular mechanisms. These findings are obtained from the databases of Web of Science, Google Scholar, PubMed, Scopus, and ResearchGate. Anticancer activities and their underlying mechanisms were mainly based on cancer cell proliferation inhibition, cell cycle arrest and apoptosis regulation, cell metastasis suppression, and immune cell activation. These effects are attributed to its bioactive components, viz. atractylenolide I, hispolon, and hispidin present in the mycelium and fruiting body. Based on our findings from the available literature, it is concluded that further comprehensive studies are required to identify all the bioactive compounds and the relationship between their structure and anticancer properties. Further, it is necessary to analyze its clinical use, safety, and efficacy alone as well as in combination with anticancer drugs. [ABSTRACT FROM AUTHOR]

Objective: To identify any adversities in the intraoperative and early postoperative outcome of right live-related donor nephrectomy. Study Design: Cross sectional study. Place and Duration of Study: Armed Forces Institute of Urology, Rawalpindi, from Jan 2013 to Jul 2015. Methodology: A total of 143 successive patients underwent open live donor nephrectomies (right=41). Perioperative outcome for both sided procedures were analyzed to identify any difference as regard the intraoperative (warm ischemia time, total duration of surgery, peroperative complications) and early postoperative parameters (days of hospitalization, complications). Results: No statistically significant difference was found in studied parameters like total operative time, the warm ischemia time, duration of hospital stay and the intra- and early postoperative complications amongst both the groups. The mean warm ischemia time was 86 ± 12 seconds (Rt) versus 90 ± 12 seconds (Lt). The mean time for surgery was 110 ± 18.1 minutes (Rt) versus 121 ± 18.2 minutes (Lt). There were only five minor complications and one major complication. Conclusion: Right live-related donor nephrectomy is equally safe and feasible option with similar intra-and postoperative complications as for left side. Therefore, whenever required, it is safe to leave the donor with a better functioning kidney. [ABSTRACT FROM AUTHOR]

Purpose: Intrafollicular fluid (IFF) melatonin plays a decisive role in maintaining granulosa cells' DNA integrity and protects them against apoptosis. It reduces oxidative stress and improves the oocyte quality with a higher fertilization rate. Method: This prospective study investigated the antioxidant property of IFF melatonin and its impact on IVF outcome parameters. We also explored the relative expression of five microRNAs (miR-663b, miR-320a, miR-766-3p, miR-132-3p, miR-16-5p) and levels of cell-free DNA (cfDNA) by real-time PCR in unexplained infertile patients. We collected 425 follicular fluid (FF) samples containing mature oocytes from 295 patients undergoing IVF. Results: Patients were subgrouped based on IFF melatonin concentration (group A ≤ 30 pg/mL, group B > 70 to ≤ 110 pg/mL, group C > 111 to ≤ 385 pg/mL). Our results showed that patients with ≤ 30 pg/mL IFF melatonin levels have significantly higher oxidative stress markers, cfDNA levels, and lower relative expression of miR-663b, miR-320a, miR-766-3p, miR-132-3p, and miR-16-5p compared to other subgroups (p < 0.001). Similarly, they have a low fertilization rate and a reduced number of high-quality day 3 embryos. Conclusion: Findings suggest that the therapeutic use of melatonin produces a considerable rise in the number of mature oocytes retrieved, fertilization rate, and good-quality embryo selection. Furthermore, miRNA signature enhances the quality of embryo selection, thus, may allow us to classify them as non-invasive biomarkers to identify good-quality embryos. [ABSTRACT FROM AUTHOR]

Cancer is known as one of the most common diseases that are associated with high mobility and mortality in the world. Despite several efforts, current cancer treatment modalities often are highly toxic and lack efficacy and specificity. However, the application of nanotechnology has led to the development of effective nanosized drug delivery systems which are highly selective for tumors and allow a slow release of active anticancer agents. Different Nanoparticles (NPs) such as the silicon-based nano-materials, polymers, liposomes and metal NPs have been designed to deliver anti-cancer drugs to tumor sites. Among different drug delivery systems, carbohydrate-functionalized nanomaterials, specially based on their multi-valent binding capacities and desirable bio-compatibility, have attracted considerable attention as an excellent candidate for controlled release of therapeutic agents. In addition, these carbohydrate functionalized nano-carriers are more compatible with construction of the intracellular delivery platforms like the carbohydrate-modified metal NPs, quantum dots, and magnetic nano-materials. In this review, we discuss recent research in the field of multifunctional glycol-nanoparticles (GNPs) intended for cancer drug delivery applications. [ABSTRACT FROM AUTHOR]

The conventional therapies for cancer have a major concern of poor accessibility to tumor tissues. Furthermore, the requirement of higher doses and non-selective nature of therapeutic are associated with a range of adverse drug reactions (ADRs). However, flavonoids are documented to be effective against various types of cancer, but they are not evaluated for their safety profile and tumor site-specific action. Low solubility, rapid metabolism and poor absorption of dietary flavonoids in gastrointestinal tract hinder their pharmacological potential. Some studies have also suggested that flavonoids may act as pro-oxidant in some cases and may interact with other therapeutic agents, especially through biotransformation. Nanocarriers can alter pharmacokinetics and pharmacodynamic profile of incorporating drug. Moreover, nanocarriers are designed for targeted drug delivery, improving the bioavailability of poorly water-soluble drugs, delivery of macromolecules to site of action within the cell, combining therapeutic agents with imaging techniques which may visualize the site of drug delivery and co-delivery of two or more drugs. Combining two or more anti-cancer agents can reduce ADRs and nanotechnology played a pivotal role in this regard. In vitro and in vivo studies have shown the potential of flavonoids nano-formulations, especially quercetin, naringenin, apigenin, catechins and fisetin in the prevention and treatment of several types of cancer. Similarly, clinical trials have been conducted using flavonoids alone or in combination, however, the nano-formulations effect still needs to be elucidated. This review focuses on the impact of flavonoids nano-formulations on the improvement of their bioavailability, therapeutic and safety profile and will open new insights in the field of drug discovery for cancer therapeutics. [ABSTRACT FROM AUTHOR]

Being a transcription factor, NF-κB regulates gene expressions involving cell survival and proliferation, drug resistance, metastasis, and angiogenesis. The activation of NF-κB plays a central role in the development of inflammation and cancer. Thus, the down-regulation of NF-κB may be an exciting target in prevention and treatment of cancer. NF-κB could act as a tumor activator or tumor suppressant decided by the site of action (organ). Polyphenols are widely distributed in plant species, consumption of which have been documented to negatively regulate the NF-κB signaling pathway. They depress the phosphorylation of kinases, inhibit NF-κB translocate into the nucleus as well as interfere interactions between NF-κB and DNA. Through inhibition of NF-κB, polyphenols downregulate inflammatory cascade, induce apoptosis and decrease cell proliferation and metastasis. This review highlights the anticancer effects of polyphenols on the basis of NF-κB signaling pathway regulation. [ABSTRACT FROM AUTHOR]

Application of green manures substitutes use of chemical fertilizers, improves soil health, prevents soil degradation also ensures food security. Two years' field experiment was laid out to determine the impact of Egyptian clover green manuring (GM) under varying nitrogen (N) levels on soil properties and maize production. Maize was grown using six N levels, i.e., 0, 50, 100, 150, 200, and 250 kg ha−1 along with GM and without GM. The GM improved grain yield (+33%, +48%) due to substantial improvement in grains/cob, 1000-grain weight and grain nutritional contents during spring 2017 and 2018 respectively. Likewise, GM also improved organic matter (OM) (+40%, +88%), available N (+210%, +219%), and total phosphorus (P) (+112%, +128%) compared to no GM. Similarly, 250 kg N ha−1 produced more grains/cob, biological yield and grain yield compared to control and other levels. In interactive effect, GM with 150 kg N ha−1 outperformed in improving 1000-grain weight, maize productivity and agronomic N efficiency. In conclusion, GM improved soil OM and total soil N compared to no GM. Moreover, GM with 150 kg N ha−1 improved productivity, agronomic N efficiency and saved 40% N compared with no GM where 250 kg N ha−1 gave best results. [ABSTRACT FROM AUTHOR]

Pain represents an unpleasant sensation linked to actual or potential tissue damage. In the early phase, the sensation of pain is caused due to direct stimulation of the sensory nerve fibers. On the other hand, the pain in the late phase is attributed to inflammatory mediators. Current medicines used to treat inflammation and pain are effective; however, they cause severe side effects, such as ulcer, anemia, osteoporosis, and endocrine disruption. Increased attention is recently being focused on the examination of the analgesic potential of phytoconstituents, such as glycosides of traditional medicinal plants, because they often have suitable biological activities with fewer side effects as compared to synthetic drugs. The purpose of this article is to review for the first time the current state of knowledge on the use of glycosides from medicinal plants to induce analgesia and anti-inflammatory effect. Various databases and search engines, including PubMed, ScienceDirect, Scopus, Web of Science and Google Scholar, were used to search and collect relevant studies on glycosides with antinociceptive activities. The results led to the identification of several glycosides that exhibited marked inhibition of various pain mediators based on different well-established assays. Additionally, these glycosides were found to induce most of the analgesic effects through cyclooxygenase and lipoxygenase pathways. These findings can be useful to identify new candidates which can be clinically developed as analgesics with better bioavailability and reduced side effects. [ABSTRACT FROM AUTHOR]

Quercetin is a flavonoid with notable pharmacological effects and promising therapeutic potential. It is widely distributed among plants and found commonly in daily diets predominantly in fruits and vegetables. Neuroprotection by quercetin has been reported in several in vitro studies. It has been shown to protect neurons from oxidative damage while reducing lipid peroxidation. In addition to its antioxidant properties, it inhibits the fibril formation of amyloid-β proteins, counteracting cell lyses and inflammatory cascade pathways. In this review, we provide a synopsis of the recent literature exploring the relationship between quercetin and cognitive performance in Alzheimer's disease and its potential as a lead compound in clinical applications. [ABSTRACT FROM AUTHOR]

Objective: Pyrus pashia has traditionally been used as a therapeutic agent including sedative. In this regard, hydroethanolic extract of Pyrus pashia (HEPP) was screened for phytochemical investigation, acute toxicity, and sedative-hypnotic activity to provide a scientific rationale to its ethno-medicinal uses.Methods: Mice were used in acute toxicity test; sedative potential was observed in open field test while thiopental-induced sleeping time and barbiturate-induced sleeping time tests were used for the assessment of hypnotic like effects of HEPP. Various phytochemical groups were detected in preliminary phytochemical tests.Results: In acute toxicity study, the extract was found safe up to 1g/kg while the extract caused 50% death at 1500 mg/kg. In all animal models, the extract had shown sedative and hypnotic effects but the most significant effect observed at increased dose in comparison with standard diazepam-treated group. In open field test, the extract at doses of 200 and 400 mg/kg, there is mild decrease in number of lines crossed by tested animals (mice) while significant reduction shown at 600 mg/kg compared with diazepam-treated group at dose 0.5 mg/kg. In phytochemical investigation HEPP subjected to different phytochemical tests. From the thoroughly study, it is revealed that these constituents mainly participating in sedation and hypnosis.Conclusions: The results of the present study showed significant sedative-hypnotic effects of the HEPP in mice and that the central benzodiazepine receptors are involved in the sedative-hypnotic effects of this plant. [ABSTRACT FROM AUTHOR]

α-glucosidase inhibition is a rational approach in the effective management of type 2 diabetes. Several inhibitors of this enzyme class are in clinical use, but are riddled with efficacy, potency and safety challenges. For this reason, new effective α-glucosidase inhibitors are under investigation. Compounds with 1, 3, 4-oxadiazole nucleus have shown preclinical efficacy as α-glucosidase inhibitors and as anti-inflammatory agents. Moreover, 1, 3, 4-oxadiazoles also play important role in pesticide chemistry, polymer science, and they are considered as the building blocks in the production of new molecular agents for bioactive molecules. In the present study, computational analyses were carried out for various 1,3,4-oxadiazole (which were divided into BF2 & BF3 series); the most active compound was taken as a potent inhibitor, and pharmacophore were formed from that compound, followed by validation against a test database. The pharmacophore-based virtual screening was performed and, by successive eliminations, six compounds of different interactions with the significant amino acid residues were selected as the lead compounds. It is concluded that these six compounds with 1, 3, 4-oxadiazoles nucleus might be used as promising drug candidates in α-glucosidase inactivation and thus we recommend further in vitro and in vivo pharmacological and safety studies. [ABSTRACT FROM AUTHOR]

In Wireless Sensor Networks (WSNs), energy-efficient routing is required to conserve the scarce resources of these networks. Various energy-efficient routing protocols have been proposed in this context. Among them, cluster-based hierarchical routing protocols are the most efficient ones. In these protocols, each sensor node, i.e., a member node, continuously captures the data from environment, stores in its buffer and waits for its allocated timeslot to transmit the data to a designated cluster head. The buffer of each node is subject to one or more pre-defined threshold values. If the buffer occupancy level exceeds the threshold value, the node starts to drop the captured data. A member node may continuously capture the data and may have to wait longer than expected to transmit it to the base station. In this context, the data generated by the underlying application may suffer excessive delay and may no longer be useful for further analysis. To address this issue, we propose a channel borrowing scheme for the member nodes within each cluster. Each member node monitors its buffer and if the occupancy level exceeds a threshold value, a channel borrowing request is initiated. Each node maintains a table of potential cluster heads. A neighboring cluster head is selected for channel borrowing, based on its signal strength. If a neighboring cluster head has a spare channel, it is allocated to the member node. The request for borrowing a channel must be acknowledged within a pre-defined threshold waiting time. The experimental results show that our propose scheme reduces packet loss, energy consumption, end-to-end delay and enhances throughput and network lifetime. [ABSTRACT FROM AUTHOR]

In addition to protecting body from infections and diseases, the immune system produces auto-antibodies that can cause complex autoimmune disorders, such as Type I diabetes, primary biliary cirrhosis, rheumatoid arthritis, and multiple sclerosis, to name a few. In such cases, the immune system fails to recognize between foreign agents and its own body cells. Different factors, such as genetic factors (CD25, STAT4), epigenetic factors (DNA methylation, histone modifications) and environmental factors (xenobiotics, drugs, hormones) trigger autoimmunity. Glucocorticoids, non-steroidal anti-inflammatory drugs (NSAIDs), immunosuppressive and biological agents are currently used to manage autoimmune diseases of different origins. However, complete cure remains elusive. Many dietary and natural products including polyphenols have been widely studied as possible alternative treatment strategies for the management of autoimmune disorders. Polyphenols possess a wide-range of pharmacological and therapeutic properties, including antioxidant and anti-inflammatory activities. As immunomodulatory agents, polyphenols are emerging pharmaceutical tools for management of various autoimmune disorders including vitiligo, ulcerative colitis and multiple sclerosis (MS). Polyphenols activate intracellular pathways such as arachidonic acid dependent pathway, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway, mitogen-activated protein kinases (MAPKs) pathway, phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway and epigenetic modulation, which regulate the host's immune response. This timely review discusses putative points of action of polyphenols in autoimmune diseases, characterizing their efficacy and safety as therapeutic agents in managing autoimmune disorders. [ABSTRACT FROM AUTHOR]

The objective of the current study is to assess the knowledge level regarding complication of diabetic neuropathy among the diabetic patients. A total 350 Diabetic patients were chosen for present study from tertiary care hospital hailing from Hyderabad Sindh and well developed Questionnaire was distributed among them. Only those subjects were included who showed their interest and returned back the filled questionnaire. Out of 300 study subjects 134 patients knew that which sort of the complication had appeared in their feet, 92 patients had answered No to question which was asked from them. Only 74 patients don't know the appearance and actual cause of the complication of neuropathy. The awareness was found more among literate patients while those who had less educational background were found to be less aware from the disease complications. Among the study subjects mostly patients do not know the actual cause of neuropathic complication and which was the complication appeared in their feet. [ABSTRACT FROM AUTHOR]

Abstract The liver is the most essential organ of the body performing vital functions. Hepatic disorders affect the physiological and biochemical functions of the body. These disorders include hepatitis B, hepatitis C, alcoholic liver disease (ALD), nonalcoholic fatty liver disease (NAFLD), liver cirrhosis, hepatic failure and hepatocellular carcinoma (HCC). Drugs related hepatotoxicity is one of the major challenges facing by clinicians as it is a leading cause of liver failure. During post-marketing surveillance studies, detection and reporting of drug-induced hepatotoxicity may lead to drug withdrawal or warnings. Several mechanisms are involved in hepatotoxicity such as cell membrane disruption, initiating an immune response, alteration of cellular pathways of drug metabolism, accumulation of reactive oxygen species (ROS), lipid peroxidation and cell death. Curcumin, the active ingredient of turmeric and exhibits therapeutic potential for the treatment of diabetes, cardiovascular disorders and various types of cancers. Curcumin is strong anti-oxidant and anti-inflammatory effects and thus it possesses hepatoprotective properties. Despite its low bioavailability, its hepatoprotective effects have been studied in various protocols of hepatotoxicity including acetaminophen, alcohol, lindane, carbon tetrachloride (CCL 4), diethylnitrosamine and heavy metals induced hepatotoxicities. This report reviews the hepatoprotective effects of curcumin with a focus on its mechanistic insights in various hepatotoxic protocols. Highlights • Hepatoxicity caused morbidity and mortality in millions of people around the world. • Drug resistance and sensitivity with the classical treatments is a great challenge need to be address. • Natural compound, curcumin has shown versatile hepatoprotective effects in different in vitro and in vivo models. • Based on documented data, it could be the drug of future as a potent hepatoprotective agent after clinical confirmation. [ABSTRACT FROM AUTHOR]

Abstract Flavonoids are natural polyphenolic compounds which are included in a panoply of drugs and used to treat and/or manage human ailments such as metabolic, cardiovascular, neurological disorders and cancer. Thus, the purpose of this review is to emphasize the importance of flavonoids for the treatment of autoimmune diseases and put into the limelight of the scientific community several health-promoting effects of flavonoids which could be beneficial for the development of novel drugs from natural products. Despite available reviews on flavonoids targeting various disease conditions, a comprehensive review of flavonoids for autoimmune diseases is still lacking. To the best of our knowledge, this is the first attempt to review the potential of flavonoids for autoimmune diseases. The structure-activity relationship of flavonoids in this review revealed that the rearrangement and introduction of other functional groups into the basic skeleton of flavonoids might lead to the development of new drugs which will be helpful in relieving the painful symptoms of various autoimmune diseases. [ABSTRACT FROM AUTHOR]

Abstract Ethnopharmacological relevance The genus Vanda (Family: Orchidaceae) comprises about 73 species mainly distributed in Southeast Asia. Plants belonging to this genus are being used in the traditional medicine systems in Asian countries specially in India, Nepal, China and Bangladesh. Aim of the review The aim of this work was to review the scientific work about medicinal orchids of the genus Vanda regarding their traditional uses, reported bioactive components, and pharmacological activities. Materials and methods The information related to traditional uses, pharmacological activities, and bioactive compounds was systematically collected from the scientific literature databases including SciFinder, Scopus, PubMed and Google Scholar, published books and conference proceedings. Results The literature survey revealed diverse traditional uses of different species of Vanda , mainly against indigestion, wounds, hepatitis, dyspepsia, bronchitis, piles, rheumatism, and bone fracture. However, only few of them are investigated scientifically for their chemical constituents and pharmacological activities. Bioactive compounds including eucomic acid derivatives, phenanthrene derivatives and other phenolic compounds are reported from Vanda species. Different extracts were so far evaluated for number of pharmacological activities including neuroprotective, anti-aging, antimicrobial, anti-inflammatory, antioxidant, membrane stabilizing, wound healing and hepato-protective activities. Conclusion Vanda spp. are of much significance as ornamental flowers, but also used widely in traditional medicines and have potential for their diverse pharmacological activities. However, many members of the genus Vanda need further detailed studies regarding chemical constituents and mechanism-based pharmacological activities. Similarly, further studies should also focus on the conservation, cultivation and sustainable utilization of these species. Graphical abstract fx1 [ABSTRACT FROM AUTHOR]

Abstract The environmental sustainability agenda is not easy to be achieved without implementing pro-growth and pro-poor growth policies across the globe. Pakistan's economy is no exception that strive hard to managed environmental resource capital and pro-poor growth expenditures in order to reduce poverty incidence and carbon mitigation policies, while many efforts need more sustainable instruments to be achieved United Nation's assigned sustainable development target till 2030. The study selected an annual time series data from 1975 to 2016 and employed two –step Generalized Method of Moments (GMM) estimator for robust inferences. The results show that higher economic growth decreases poverty incidence through social reforms, while, deforestation, under −5 mortality rate, trade openness, carbon emissions, and FDI inflows largely increases poverty incidence in a country. The study confirmed Environmental Kuznets Curve (EKC) hypothesis of carbon emissions in relation of per capita income and public spending on education, while 'pollution haven hypothesis' is confirmed due to high involvement of dirty polluting industries in country's economic transformation process. The fossil fuel combustion and high population density increases carbon emissions that sabotage the process of sustainable development in a country. Thus, it is imperative to device sustainable policies for mitigating carbon-fossil emissions with cleaner production techniques and improves the quality of life of poor people through increase social expenditures that trickle down to the poor as compared to the non-poor. Highlights • To assess the twin agenda of pro-poor growth and sustainable development in Pakistan. • Higher economic growth decreases poverty incidence through social reforms. • Deforestation, under −5 mortality, trade, CO2 emissions, and FDI increases poverty incidence. • The EKC hypothesis of CO2 emissions is found with income and education. • The 'pollution haven hypothesis' is confirmed in a country. [ABSTRACT FROM AUTHOR]

Objective: To assess and find out the events of medication errors and to classify the medication error in the diabetology and general medicine department. Study Design: The longitudinal cohort prospective observational study. Place and Duration of Study: Diabetes and general medicine department of Chandka Medical College Hospital larkana from Jan 2017 to May 2017. Material and Methods: Data was gathered from 1255 prescriptions of both inpatient and outpatient department of diabetology and general medicine after ensuring the ethical approval. This prospective observational study was made in tertiary care chandka medical college hospital larkana. Results: Male 730 (58.10%) and 525 (41.8%) Females and medication error recorded was 513 to both genders .In male 289 (56.3%) errors and in females 224 (43.7%) prescriptions were found. Conclusion: From the present study the conclusion can be made that there is huge ratio of medication error in practice and the possible contributors of medication deviation are incorrect dosage forms, incorrect strengths, lack of diabetes counseling and others. Pharmacist is the key role to prevent such errors. [ABSTRACT FROM AUTHOR]

Objective: To explore the qualities of brilliant surgeons that makes them distinctive. Study Design: A qualitative exploratory study. Place and Duration of Study: The study was conducted in Armed Forces Hospitals, Rawalpindi, from Jan to Jul 2017. Material and Methods: A purposive sampling technique was applied for in-depth, semi-structured interviews of 19 members (ten surgeons, six anesthesiologists and three operation room assistants) having experience of surgical environment for more than 20 years in different institutions. Computer Assisted Qualitative Data Analysis Software (CAQDAS) was employed for thematic data analysis using software NVIVO 11 Pro. Results: Study participants reported observation of distinctive personality characteristics of a few surgeons hitherto termed as “brilliant”. Multifaceted aspects of their personality were identified and categorized into five major themes: mental, psychological and emotional, social, mechanical, and structural strength. The first three themes were found to be common among brilliant achievers in all other professions as well, however, the mechanical and structural strength domains were considered to have unique and substantial bearing on the achievement of brilliance in surgery. Conclusion: A category amongst the surgeon has been identified and termed as “brilliant”. These brilliant surgeons were gifted in five domains of their personality with a distinct set of qualities which made them outclass their contemporaries. [ABSTRACT FROM AUTHOR]

Abstract Fungal diseases could be serious and, in some cases, life-threatening. Considering the limited availability of antifungal agents in use, and the emergence of multi drug resistance (MDR) in fungal infections, there is a pressing need for the development of novel broad spectrum antifungal drugs with better efficacy. Coruscanone A analogues, natural derivatives which target the fungal lanosterol enzyme, were docked against lanosterol 14 α-demethylase (CYP51A1) that converts lanosterol to 4,4-dimethylcholesta-8,14,24-trien-3β-ol in the ergosterol biosynthesis pathway in order to stabilize the plasma membrane of the fungal species, and hence can be targeted for an effective antifungal therapy. For this purpose, we have employed Glide docking, using MAESTRO to predict binding modes of these Coruscanone (A) analogs to the enzyme. Results showed that some of these compounds were potent inhibitors of this enzyme compared to fluconazole (the known ligand of the enzyme that was used as control in the study) as evidenced by their docking scores and binding interactions. In conclusion, these finding may be helpful in the design of new effective and potent antifungal inhibitors. Graphic abstract Unlabelled Image [ABSTRACT FROM AUTHOR]

Depression, a multifactorial brain disorder, is one of the most prevalent diseases worldwide. Several strategies have been developed to counteract the main symptoms and disorders. However, the treatments are usually associated with different side effects or poor effect. For that reason, new necessary approaches are emerging; among them, natural products are good alternatives since no interactions have been described up to now. Flavonoids have been related to antidepressant effects in cell lines and animal models by their action on the amine mechanisms protecting the neuroendocrine and immune systems. The current review includes an approach of some of the main results related to the action of flavonoids on depression found in the literature and a short view of the possible mechanisms involved. Thus, it highlights the potential emerging candidates with strong antidepressant effects which could be effective new compounds. [ABSTRACT FROM AUTHOR]

Poor pharmacokinetic and safety profiles create significant hurdles in the drug development process. This work focuses on a detailed understanding of drug discovery interplay among physicochemical, pharmacokinetic, toxicity endpoints, and antioxidant properties of oxindole derivatives. DFT compıutations were also performed at B3LYP/6-311G** level to evaluate the physicochemical properties, global reactivity features, and intramolecular interactions. The BOILED-Egg pharmacokinetic model envisaged gastrointestinal absorption, blood-brain barrier penetration, and no interaction with p-glycoprotein for compounds C1 and C2. The physicochemical evaluation revealed that C1 possesses superior drug-like properties fit for oral absorption. Both derivatives were predicted to have high plasma protein binding, efficient distribution, and inhibiting CYP 450 major isoforms but serve as substrates only for a few of them. Both molecules have mild to moderate clearance rates. Out of ten toxicity parameters, only hepatotoxicity was predicted. DFT results implied that the meta position of the -OH group made the possibility of charge transfer greater than -para positioned -OH, due to the ΔN max (eV) values of molecules C1 and C2 being calculated at 2.596 and 2.477, respectively. Both C1 and C2 exhibited a concentration dependant DPPH and ABTS radical scavenging activity. The chemical structure-physicochemical-pharmacokinetic relationship identified the meta position as the favorite for the electron-withdrawing hydroxyl group. This provides useful insight to medicinal chemists to design 6-chlorooxindole derivatives with an acceptable drug-like and pharmacokinetic property. [Display omitted] • Drug discovery is an interplay among physicochemical, pharmacokinetic, toxicity, and biological activities. • DFT studies are important for physicochemical properties, global reactivity features, and intramolecular interactions. • Oxindole derivatives possess acceptable drug like pharmacokinetic properties. • Oxindole derivatives exhibited a concentration dependant DPPH and ABTS radical scavenging activity. • Chemical structure-physicochemical-pharmacokinetic relationship identified the meta position as favorite for derivatization. [ABSTRACT FROM AUTHOR]

Alkaloids are well-studied secondary metabolites, with recent preclinical studies evidencing that many of them exhibit anti-cancer, anti-depressant, anti-nociceptive, anti-inflammatory, anti-pyretic, anti-platelet, anti-oxidant, and anti-bacterial properties. Aconitum is a genus rich of diverse alkaloids. More than 450 alkaloids have been identified in a variety of species. Songorine is a C 20 diterpenoid alkaloid and 12-keto analog of napelline, isolated from Aconitum soongaricum and was associated with a heterogeneous panel of biological functions. However, the bioactivity profile of this natural product has not been reviewed up to now. The present manuscript aims to summarize the most important biological activities associated with songorine administration in preclinical models. The most significant data found in the scientific literature were evaluated in order to summarize the potential clinical utility of songorine in a diverse spectrum of pathologies and conditions. Songorine and its derivatives have many pharmacological effects including anti-arrhythmic, anti-cardiac-fibrillation, excitation of synaptic transmission, anxiolytic effects, anti-nociceptive, anti-inflammatory, anti-arthritis effects, and a regenerative effect in a skin excision wound animal model. Despite its outstanding pharmacotherapeutic potential, songorine has never been tested in clinical trials. Therefore, further evaluation is required to better evaluate its clinical utility. [ABSTRACT FROM AUTHOR]

Inflammation comprises the reaction of the body to injury, in which a series of changes of the terminal vascular bed, blood, and connective tissue tends to eliminate the injurious agent and to repair the damaged tissue. It is a complex process, which involves the release of diverse regulatory mediators. The current anti-inflammatory agents are challenged by multiple side effects and thus, new effective therapies are highly needed. The aim of this review is to summarize the described microsomal prostaglandin E synthase-1 (mPGES-1) inhibitors or transcriptional suppressors from medicinal plants, which could be an ideal approach in the management of inflammatory disorders, but need further clinical trials in order to be ultimately validated. [ABSTRACT FROM AUTHOR]

Background Acetylcholinesterase (AChE), a serine hydrolase, is primarily responsible for the termination of signal transmission in the cholinergic system, owing to its outstanding hydrolyzing potential. Its substrate acetylcholine (ACh), is a neurotransmitter of the cholinergic system, with a predominant effect on motor neurons involved in memory formation. So, by decreasing the activity of this enzyme by employment of specific inhibitors, a number of motor neuron disorders such as myasthenia gravis, glaucoma, Lewy body dementia, and Alzheimer’s disease, among others, can be treated. However, the current-available AChE inhibitors have several limitations in terms of efficacy, therapeutic range, and safety. Scope and approach Primarily due to the non-compliance of current therapies, new, effective and safe inhibitors are being searched for, especially those which act through multiple receptor sites, but do not elicit undesirable effects. In this regard, the evaluation of phytochemicals such as flavonoids, can be a rational approach. The therapeutic potential of flavonoids has already been recognized agaisnt several ailments. This review deals with various plant-derived flavonoids, their preclinical potential as AChE inhibitors, in established assays, possible mechanisms of action, and structural activity relationship (SAR). Results and conclusions Subsequently, a number of plant-derived flavonoids with outstanding efficacy and potency as AChE inhibitors, the mechanistic, their safety profiles, and pharmacokinetic attributes have been discussed. Through derivatization of these reported flavonoids, some limitation in efficacy or pharmacokinetic parameters can be addressed. The selected flavonoids ought to be tested in clinical studies to discover new neuro-therapeutic candidates. [ABSTRACT FROM AUTHOR]

Androgen mediating signaling is implicated in regulating the expression of reproductive related genes. Any deviation in the gene expression might be the ignitable precursor for genomic instability that inflames the genomic rearrangements and a leading cause of cancer. The main goal of this study was to determine the relationships between trinucleotide repeats of androgen receptor (AR), sex steroids, and sexual function in men presenting with reduced sperm motility. We investigated the singleton or combinatorial effects of the length of trinucleotide repeats of AR on reproductive hormones, clinical parameters, semen analyses, as well as sexual assessment function of 210 asthenospermic outpatients along with 125 normal subjects. Sexual assessment was executed using the International Index of Erectile Function (IIEF-15 score) which measures erectile function (EF), orgasmic function (OR), sexual desire (SD), intercourse satisfaction (IS), and overall satisfaction. Our findings suggest that long (>26 CAG)n repeats have an inverse correlation with circulatory FSH and T, whereas long (>25 GGC)n repeats have moderated affiliation with reduced sperm concentration. The study revealed a novel finding by exploring the negative correlation between elongated (CAG)n repeats and the cumulative IIEF-15 score, orgasm function (OR), and erectile function (EF) in asthenospermic men. This study examines the tri-nucleotide correlation with sexual function in Punjabi men enhancing our understanding of the regulatory mechanisms of sexual performance.Abbreviations: AR: androgen receptor; IIEF-15 score: International Index of Erectile Function; EF: erectile function; OR: orgasmic function; SD: sexual desire; IS: intercourse satisfaction; FSH: follicular stimulating hormone; T: testosterone; NTD: N-terminal transactivation domain; DBD: DNA-binding domain; LBD: ligand binding domain; TNR: tri-nucleotide repeat [ABSTRACT FROM AUTHOR]

Current therapies in clinical practice face strong criticism regarding their efficacy, and side effects, which forced the neuro-researchers to discover novel agents with different mechanistic insights. Glycosides are naturally-occurring plant secondary metabolites with significant medicinal potential and clinical scope as antidepressant. The aim of this review is to focus on the antidepressant effects of glycosides in preclinical studies, with an emphasis on the possible mechanisms. The literature search revealed that only a few phytoglycosides have been evaluated for their relevance in depression alleviation. Through preclinical tests, it has come forth that the efficacy is mediated by the modulation of brain-derived neurotrophic factor (BDFN) in the hippocampus, that is known for promoting synaptic efficacy, neuronal connectivity and neuroplasticity. Thus, attempting the upregulation of BDNF expression by plant glycosides can be a novel therapeutic strategy for the treatment of depression. The outcome of this review can stimulate neuroscientists to evaluate plant-derived glycosides for the treatment of depression, as these structurally-complex and diverse molecules, might usher in a new paradigm in the treatment of depression, with a better efficacy and tolerability. [ABSTRACT FROM AUTHOR]

Neurodegenerative disorders (NDDs) such as Alzheimer’s and Parkinson’s diseases are the most common age-related pathologies that affect millions of people all over the world. To date, effective therapy for NDDs is not available and current approaches to disease management include neuroprotection strategy with a hope of maintaining and enhancing the function of survising neurons. Of course, such an approach by its own will not offer a cure but is likely to delay the disease progression by ameliorating the increase of neurotoxic agents such reactive oxygen species (ROS) as well as the associated inflammatory cascades. In this regard, natural products including flavonods that offer neuroprotection through multiple mechanisms have gained a lot of interest in recent years. In this communication, evidences from the various experimental models and clinical trials on the therapeutic potential of one promising flavonod, apigenin, is presented. Its chemistry, mechanism of action and potential benefits in the various examples of NDDs are discussed in the light of drug discovery aspects. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is a metabolic disorder in which the glucose level in blood exceeds beyond the normal level. Persistent hyperglycemia leads to diabetes late complication and obviously account for a large number of morbidity and mortality worldwide. Numerous therapeutic options are available for the treatment of diabetes including insulin for type I and oral tablets for type II, but its effective management is still a dream. To date, several options are under investigation in various research laboratories for efficacious and safer agents. Of them, peptides are currently amongst the most widely investigated potential therapeutic agents whose design and optimal uses are under development. A number of natural and synthetic peptides have so far been found with outstanding antidiabetic effect mediated through diverse mechanisms. The applications of new emerging techniques and drug delivery systems further offer opportunities to achieve the desired target outcomes. Some outstanding peptides in preclinical and clinical studies with better efficacy and safety profile have already been identified. Further detail studies on these peptides may therefore lead to significant clinically useful antidiabetic agents. [ABSTRACT FROM AUTHOR]

The aim of this study is to examine the impact of air pollutants, including mono-nitrogen oxides (NOx), nitrous oxide (N 2 O), sulfur dioxide (SO 2 ), carbon dioxide emissions (CO 2 ), and greenhouse gas (GHG) emissions on ecological footprint, habitat area, food supply, and biodiversity in a panel of thirty-four developed and developing countries, over the period of 1995–2014. The results reveal that NOx and SO 2 emissions both have a negative relationship with ecological footprints, while N 2 O emission and real GDP per capita have a direct relationship with ecological footprints. NOx has a positive relationship with forest area, per capita food supply and biological diversity while CO 2 emission and GHG emission have a negative impact on food production. N 2 O has a positive impact on forest area and biodiversity, while SO 2 emissions have a negative relationship with them. SO 2 emission has a direct relationship with per capita food production, while GDP per capita significantly affected per capita food production and food supply variability across countries. The overall results reveal that SO 2 , CO 2 , and GHG emissions affected potential habitat area, while SO 2 and GHG emissions affected the biodiversity index. Trade liberalization policies considerably affected the potential habitat area and biological diversity in a panel of countries. [ABSTRACT FROM AUTHOR]