Antibacterial effect of red laser-activated silver nanoparticles synthesized with grape seed extract against Staphylococcus aureus and Escherichia coli.

Living organisms, particularly humans, frequently encounter microorganisms such as bacteria, fungi, and viruses in their surroundings. Silver nanoparticles are widely used in biomedical devices because of their antibacterial and antiviral properties. The study evaluates the efficacy of red laser and silver nanoparticles from grape seed extract (AgNPs-GSE) in reducing Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus bacteria, which cause infections. The sample comprised three groups: a control group without laser irradiation (T0), Escherichia coli samples (A1 and A2) irradiated with a 405-nm diode laser at different times and concentrations of silver nanoparticles, and Staphylococcus aureus samples (A3 and A4) illuminated with a 405-nm diode laser at different times and concentrations. Bacteria in groups A2 and A4 were treated with a photosensitizer (PS) made from grape seed extracts, incubated for 10 min, and then irradiated for 90, 120, 150, and 180 s. The samples were cultured on TSA media, set at 37 °C, counted using a Quebec colony counter, and analyzed using ANOVA and Tukey tests with a significance level of p < 0.05. The study illustrated that the combination of 10 µl of AgNPs-GSE, exposure to a red laser at 405 nm, and an energy density of 3.44 J/cm2 effectively photoinactivated both Escherichia coli and Staphylococcus aureus bacteria. For Escherichia coli bacteria irradiated for 180 s with concentrations of 1 mM, 1.5 mM, and 2 mM AgNPs-GSE, bacterial viability decreased by 64.50%, 70.74%, and 79.53%, respectively. Similarly, Staphylococcus aureus bacteria, subjected to irradiation for 180 s with concentrations of 1 mM, 1.5 mM, and 2 mM AgNPs-GSE, demonstrated reductions in bacterial viability by 70.23%, 73.47%, and 85.04%, respectively. The findings from the present study indicate that at an energy density of 3.44 J/cm2, it was possible to inactivate Escherichia coli by 79.53% and Staphylococcus aureus by 85.04%.

Fluorescent microscopy evaluation of diode laser effect on the penetration depth of turmeric (Curcuma longa) extract cream on skin tissues of Wistar rats.

The study investigates the effect of diode laser exposure on curcumin's skin penetration, using turmeric extraction as a light-sensitive chemical and various laser light sources. It uses an in vivo skin analysis method on Wistar strain mice. The lasers are utilized at wavelengths of 403 nm, 523 nm, 661 nm, and 979 nm. The energy densities of the lasers are 20.566 J/cm2, 20.572 J/cm2, 21.162 J/cm2, and 21.298 J/cm2, which are comparable to one another. The experimental animals were divided into three groups: base cream (BC), turmeric extract cream (TEC), and the combination laser (L), BC, and TEC treatment group. Combination light source (LS) with cream (C) was performed with 8 combinations namely 523 nm ((L1 + BC) and (L1 + TEC)), 661 nm ((L2 + BC) and (L2 + TEC)), 403 nm ((L3 + BC) and (L3 + TEC)), and 979 nm ((L4 + BC) and (L4 + TEC)). The study involved applying four laser types to cream-covered and turmeric extract-coated rat skin, with samples scored for analysis. The study found that both base cream and curcumin cream had consistent pH values of 7-8, within the skin's range, and curcumin extract cream had lower viscosity. The results of the statistical analysis of Kruskal-Wallis showed a significant value (p < 0.05), which means that there are at least two different laser treatments. The results of the post hoc analysis with Mann-Whitney showed that there was no significant difference in the LS treatment with the addition of BC or TEC when compared to the BC or TEC treatment alone (p > 0.05), while the treatment using BC and TEC showed a significant difference (p < 0.05). Laser treatment affects the penetration of the turmeric extract cream into the rat skin tissue.

Bacterial metabolic engineering for the production of second-generation (2 G) bioethanol and biobutanol; a review.

The second generation (2 G) biofuels were introduced to solve the issues associated with first-generation biofuel (dependency on food materials) and fossil fuels, such as reservoirs diminution, high demand, price fluctuation, and lethal greenhouse gases emission. Butanol and ethanol are the main 2 G biofuels. They are used as a disinfectant, antiseptic, and chemical solvent in the pharmaceutical, plastic, textiles, cosmetics, and fuel industries. Currently, their bacterial biological production from lignocellulosic material at the industrial level with primitive microorganisms is under development and not economical and qualitative compatible as compared to that of fossil origin, due to the slow growth rate, low titer, recalcitrant nature of lignocellulose, strain intolerance to a higher amount of butanol and ethanol, and strain inability to tolerate inhibitors accumulated during pretreatment of lignocellulosic materials. Therefore, metabolic engineering strategies such as redirection of carbon flux, knocking out competing pathways, enhancing strain robustness and wide range of substrate utilization ability, and overexpression of enzymes involved in their biological synthesis have been applied to bacteria for enhancing their ability for 2 G ethanol and butanol production in a highly cost-effective amount from lignocellulosic materials. Herein, we summarized and reviewed the progress in metabolic engineering of bacterial species such as Clostridium spp,Escherichia coli, and Zymomonas mobilis for the synthesis of 2 G butanol and ethanol, especially from lignocellulosic materials.

Introducing sorghum DREB2 gene in maize (Zea mays L.) to improve drought and salinity tolerance.

Salinity and drought are significant abiotic stresses causing a considerable loss of seed and biomass yield in most commercial crops. Some of the most critical players in the abscisic acid pathway are drought responsive element binding (DREB) proteins that are a part of AP2/ethylene response factor transcription factors that bind to promoters of some family genes needed to be expressed under abiotic stresses. In this study, salt- and drought-tolerant maize plants were produced from immature maize embryos bombarded by the sorghum (Sorghum bicolor L.) DREB2 gene that is linked to hygromycin resistance (hpt) genes. The putative transgenic calli were transferred to an N6 medium containing 1 mg/L benzylaminopurine and 50 mg/L hygromycin. Regeneration was completed after 4 weeks on selective media under a 16/8 h light/dark condition at 25°C. Polymerase chain reaction (PCR) and reverse transcription-PCR approved the existence of upstream promoter (rd29a), hpt gene, and the expression of the DREB2 in transgenes up to the third generation (T2). It was found that the K+/Na+ ratio and the amount of proline as a screening indicator were higher in transgenic plants compared to their wild types. This result is a promising model to enhance maize tolerance to abiotic stressors.

The moderating effects of nurses' background characteristics on the relationship between family-centred care perception and practice for hospitalized children and their families in Malawi.

PURPOSE: Globally, limited information is available on the relationship between the perception and practice of family-centered care (FCC), and the moderating effects of nurses' background characteristics on this relationship. This study investigated the relationship between FCC perception and FCC practice and the moderating effects of the nurses' background characteristics on this relationship. DESIGN AND METHODS: A cross-sectional study was conducted using a two-stage stratified sampling method. Data were collected from 444 nurses using the Family Centered Care Questionnaire-Revised and analyzed using IBM SPSS Version 25. The Hayes PROCESS macro model, version 3, was integrated into SPSS to examine the moderating effects at a significance level of 0.05. RESULTS: The response rate was 98%, and a statistically significant positive association was found between FCC perception and FCC practice (r = 0.353, p < .001). Gender of a nurse (ΔR2 = 0.0206, p < .002), having children (ΔR2 = 0.0231, p < .001), experience (ΔR2 = 0.0107, p = .028), and working in a medical-surgical ward (ΔR2 = 0.0208, p = .008) had a statistically significant moderating effect on the relationship between FCC perception and FCC practice. CONCLUSION: These findings provide minimal evidence of the existence of non-modifiable moderators of FCC. Future studies with modifiable moderators are therefore needed. PRACTICE IMPLICATIONS: Understanding the moderating effects of nurses' background characteristics on the relationship between FCC perception and FCC practice may facilitate the development of FCC interventions that favor these background characteristics and facilitate the integration of FCC into routine policies and practices.

Efficacy Of Common Salt Application On The Umbilical Granuloma In Infants.

The objective of this study was to determine the efficacy of the application of common plain salt for the treatment of umbilical granuloma in infants. The study design was descriptive case series and was conducted over a period of 12 months at the paediatric unit, Mardan Medical Complex, Mardan, Pakistan. For this study a total of 50 infants with clinically evident umbilical granuloma were selected. Application of a pinch of common plain salt was advised on the granuloma twice a day for three consecutive days. Outcomes in the shape of complete resolution of the granuloma, adverse effects, and recurrence of granuloma were assessed. The number of patients responding well to the treatment was 45 (90%). The treatment showed good response and there was not any adverse effect or recurrence. It was concluded that the common plain salt is a simple, effective, safe, and cheaper option for the treatment of umbilical granuloma in infants.

Metal-Organic Frameworks Derived Electrocatalysts for Oxygen and Carbon Dioxide Reduction Reaction.

The increasing demands of energy and environmental concerns have motivated researchers to cultivate renewable energy resources for replacing conventional fossil fuels. The modern energy conversion and storage devices required high efficient and stable electrocatalysts to fulfil the market demands. In previous years, we are witness for considerable developments of scientific attention in Metal-organic Frameworks (MOFs) and their derived nanomaterials in electrocatalysis. In current review article, we have discussed the progress of optimistic strategies and approaches for the manufacturing of MOF-derived functional materials and their presentation as electrocatalysts for significant energy related reactions. MOFs functioning as a self-sacrificing template bid different benefits for the preparation of metal nanostructures, metal oxides and carbon-abundant materials promoting through the porous structure, organic functionalities, abundance of metal sites and large surface area. Thorough study for the recent advancement in the MOF-derived materials, metal-coordinated N-doped carbons with single-atom active sites are emerging candidates for future commercial applications. However, there are some tasks that should be addressed, to attain improved, appreciative and controlled structural parameters for catalytic and chemical behavior.

Dosimetric properties of thermoluminescent NaCl pellets from Khewra Salt Mines, Pakistan.

Thermoluminescence (TL) and extended dosimetric characteristics of naturally occurring sodium chloride (NaCl) salt were studied. Pellets were prepared from mined crystalline salt obtained from Khewra Salt Mines, Pakistan and irradiated from 1 mGy to 10,000 mGy using cobalt-60 gamma source. The TL response showed two dominant peaks around 125°C and 230°C, respectively, at low doses, with an additional peak in between at doses beyond 300 mGy. A linear and supra-linear TL response was observed between 1 mGy-100 mGy and 100 mGy-10 Gy dose ranges, respectively. During the first 24 h post-irradiation, the TL intensity dropped by 20%. A maximum angular dependence of up to 50% was observed between 0° to 360°. For photon energies between 33 keV and 1.25 MeV significant energy dependence was observed for photons < 100 keV only. Sample sensitivity increased with dose a qualitatively similar behaviour to TLD-200. Effective atomic number (Zeff ) of the sample (14.6) was comparable to TLD-200 (16.3). No significant dose rate effects (deviation for a cobalt-60 source within 3.5%) on the TL sensitivity of the sample were found. The lowest detectable dose limit (LDDL) for salt sample was found to be 0.8 mGy whereas the sample reproducibility test showed a maximum of ±11% deviation from the first value.

Long-term follow-up of children with neuroblastoma receiving radiotherapy to metastatic lesions within the German Neuroblastoma Trials NB97 and NB 2004.

PURPOSE: Neuroblastoma (NB) is the most common extracranial solid malignancy during childhood. Despite a multimodal treatment approach, the prognosis of patients with metastatic NB is not satisfactory. Although radiotherapy (RT) has become an integral part of treatment of the primary tumor, the role of RT in osteomedullary lesions is not well defined. A retrospective analysis was conducted to evaluate the impact of RT for metastatic sites in children with high-risk NB. METHODS: All patients with stage 4 NB from the prospective, multicenter NB trials NB97 and NB2004 who received RT to metastatic sites during frontline treatment were included in this retrospective analysis. RESULTS: A total of 18 children were irradiated with a median dose of 36 Gray (Gy; range 20-45 Gy) to one or more (range 1-3) osteomedullary metastases with or without concomitant RT to the primary tumor site. The median follow-up time was 149 months (range 55-220) in survivors. At 5 years, local relapse-free survival (LRFS) at irradiated metastatic sites and metastases-free survival (MFS) at distant, non-irradiated site rates were 51.4 and 39.9%, respectively. The estimated overall survival (OS) rate at 5 years was 49.4%. No high-grade acute or late toxicity and no secondary malignancy was reported. CONCLUSION: RT to metastases is feasible for patients with stage 4 NB. However, an impact of RT to residual metastatic sites on outcome was not found. Studies with larger cohorts or prospective trials would be desirable in order to elucidate the role of RT for metastases.

Microglial IL-10 and ß-endorphin expression mediates gabapentinoids antineuropathic pain.

Gabapentinoids are recommended first-line treatments for neuropathic pain. They are neuronal voltage-dependent calcium channel α2δ-1 subunit ligands and have been suggested to attenuate neuropathic pain via interaction with neuronal α2δ-1 subunit. However, the current study revealed their microglial mechanisms underlying antineuropathic pain. Intrathecal injection of gabapentin, pregabalin and mirogabalin rapidly inhibited mechanical allodynia and thermal hyperalgesia, with projected ED50 values of 30.3, 6.2 and 1.5 µg (or 176.9, 38.9 and 7.2 nmol) and Emax values of 66%, 61% and 65% MPE respectively for mechanical allodynia. Intrathecal gabapentinoids stimulated spinal mRNA and protein expression of IL-10 and ß-endorphin (but not dynorphin A) in neuropathic rats with the time point parallel to their inhibition of allodynia, which was observed in microglia but not astrocytes or neurons in spinal dorsal horns by using double immunofluorescence staining. Intrathecal gabapentin alleviated pain hypersensitivity in male/female neuropathic but not male sham rats, whereas it increased expression of spinal IL-10 and ß-endorphin in male/female neuropathic and male sham rats. Treatment with gabapentin, pregabalin and mirogabalin specifically upregulated IL-10 and ß-endorphin mRNA and protein expression in primary spinal microglial but not astrocytic or neuronal cells, with EC50 values of 41.3, 11.5 and 2.5 µM and 34.7, 13.3 and 2.8 µM respectively. Pretreatment with intrathecal microglial metabolic inhibitor minocycline, IL-10 antibody, ß-endorphin antiserum or µ-opioid receptor antagonist CTAP (but not κ- or δ-opioid receptor antagonists) suppressed spinal gabapentinoids-inhibited mechanical allodynia. Immunofluorescence staining exhibited specific α2δ-1 expression in neurons but not microglia or astrocytes in the spinal dorsal horns or cultured primary spinal cells. Thus the results illustrate that gabapentinoids alleviate neuropathic pain through stimulating expression of spinal microglial IL-10 and consequent ß-endorphin.

Thermoluminescence study of pellets prepared using NaCl from Khewra Salt Mines in Pakistan.

In this study, the thermoluminescence characteristics of naturally occurring salt (NaCl) were assessed for the development of a radiation dosimeter. For this purpose, mined crystalline samples of salt were procured directly from Khewra salt mines in Pakistan. The samples were hand crushed, sieved, and compressed to pellets comparable in size to standard TLD chips, and irradiated to gamma radiation doses in the range of 5 mGy and 5000 mGy. Thermoluminescence (TL) response showed three main peaks in the glow curve around 115-130 °C, 150-170 °C, and 220-240 °C. A linear TL response was observed for the dose range of 5-100 mGy. The TL response became supra-linear for the dose ranges of 100-1000 mGy and 1000-5000 mGy. The Tm-Tstop method was applied to identify the overlapping peaks of the glow curve. Computerized glow curve deconvolution (CGCD) was then employed for the characterization of electron trap parameters such as frequency factor (s), activation energy (E), and the kinetic order (b), using General Order (GO) kinetics. The figure-of-merit (FOM) was found to be 1.08%, 0.94%, 0.77%, and 0.75%, at 500 mGy, 1 Gy, 2 Gy, and 5 Gy, respectively. The TL intensity faded by 20% within the first 24 h after irradiation and finally stabilized after two weeks. In addition, structural, morphological, and elemental analyses, were also performed using various analytical techniques. X-ray diffraction (XRD) showed that the salt crystallizes in a face-centered cubic structure. Scanning electron microscope (SEM) micrographs indicated that the crystallites are closely packed and cubic-shaped with non-uniform size, and mostly found in the agglomerated form. Similarly, the elemental analysis confirmed the presence of impurities such as Mg, Sr, S, K, O, and Ca, in the samples. The present study concludes that the pellets made from salt samples from Khewra mines have a potential for use as radiation dosimeters.

Microglial Activation of GLP-1R Signaling in Neuropathic Pain Promotes Gene Expression Adaption Involved in Inflammatory Responses.

Background: Neuropathic pain is a common chronic pain, which is related to hypersensitivity to stimulus and greatly affects the quality of life of patients. Maladaptive gene changes and molecular signaling underlie the sensitization of nociceptive pathways. We previously found that the activation of microglial glucagon-like peptide 1 receptor (GLP-1R) could potently relieve formalin-, bone cancer-, peripheral nerve injury-, and diabetes-induced pain hypersensitivity. So far, little is known about how the gene profile changes upon the activation of GLP-1R signaling in the pathophysiology of neuropathic pain. Methods: Spinal nerve ligation (SNL) was performed to induce neuropathic pain in rats. Mechanical allodynia was assessed using von Frey filaments. The expression of IL-10, ß-endorphin, and µ-opioid receptor (MOR) was examined by real-time quantitative polymerase chain reaction (qPCR) and whole-cell recording. Measurements of cellular excitability of the substantia gelatinosa (SG) neurons by whole-cell recording were carried out. R packages of differential gene expression analysis based on the negative binomial distribution (DESeq2) and weighted correlation network analysis (WGCNA) were used to analyze differential gene expression and the correlated modules among GLP-1R clusters in neuropathic pain. Results: The GLP-1R agonist, exenatide, has an antiallodynic effect on neuropathic pain, which could be reversed by intrathecal injections of the microglial inhibitor minocycline. Furthermore, differential gene expression analysis (WGCNA) indicated that intrathecal injections of exenatide could reverse the abnormal expression of 591 genes in the spinal dorsal horn induced by nerve injury. WGCNA revealed 58 modules with a close relationship between the microglial GLP-1R pathway and features of nerve injuries, including pain, ligation, paw withdrawal latency (PWL), and anxiety. The brown module was identified as the highest correlated module, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that inflammatory responses were most correlated with PWL. To further unravel the changes of hyperalgesia-related neuronal electrophysiological activity mediated by microglia GLP-1 receptors, whole-cell recording identified that MOR agonism stimulated a robust outward current in the sham groups compared with the spinal nerve ligation (SNL) groups. This inhibitory effect on the SNL group was more sensitive than that of the sham group after bath application of ß-endorphin. Conclusions: Our results further confirmed that the GLP-1R pathway is involved in alleviating pain hypersensitivity mediated by spinal microglia activation, and inflammatory responses were the most correlated pathway associated with PWL changes in response to exenatide treatment. We found that the identification of gene regulation in response to GLP-1R activation is an effective strategy for identifying new therapeutic targets for neuropathic pain. Investigation for the activation of spinal microglial GLP-1R which might ameliorate inflammatory responses through gene expression and structural changes is providing a potential biomarker in pain management.

The spinal microglial IL-10/ß-endorphin pathway accounts for cinobufagin-induced mechanical antiallodynia in bone cancer pain following activation of α7-nicotinic acetylcholine receptors.

BACKGROUND: Cinobufagin is the major bufadienolide of Bufonis venenum (Chansu), which has been traditionally used for the treatment of chronic pain especially cancer pain. The current study aimed to evaluate its antinociceptive effects in bone cancer pain and explore the underlying mechanisms. METHODS: Rat bone cancer model was used in this study. The withdrawal threshold evoked by stimulation of the hindpaw was determined using a 2290 CE electrical von Frey hair. The ß-endorphin and IL-10 levels were measured in the spinal cord and cultured primary microglia, astrocytes, and neurons. RESULTS: Cinobufagin, given intrathecally, dose-dependently attenuated mechanical allodynia in bone cancer pain rats, with the projected Emax of 90% MPE and ED50 of 6.4 µg. Intrathecal cinobufagin also stimulated the gene and protein expression of IL-10 and ß-endorphin (but not dynorphin A) in the spinal cords of bone cancer pain rats. In addition, treatment with cinobufagin in cultured primary spinal microglia but not astrocytes or neurons stimulated the mRNA and protein expression of IL-10 and ß-endorphin, which was prevented by the pretreatment with the IL-10 antibody but not ß-endorphin antiserum. Furthermore, spinal cinobufagin-induced mechanical antiallodynia was inhibited by the pretreatment with intrathecal injection of the microglial inhibitor minocycline, IL-10 antibody, ß-endorphin antiserum and specific µ-opioid receptor antagonist CTAP. Lastly, cinobufagin- and the specific α-7 nicotinic acetylcholine receptor (α7-nAChR) agonist PHA-543613-induced microglial gene expression of IL-10/ß-endorphin and mechanical antiallodynia in bone cancer pain were blocked by the pretreatment with the specific α7-nAChR antagonist methyllycaconitine. CONCLUSIONS: Our results illustrate that cinobufagin produces mechanical antiallodynia in bone cancer pain through spinal microglial expression of IL-10 and subsequent ß-endorphin following activation of α7-nAChRs. Our results also highlight the broad significance of the recently uncovered spinal microglial IL-10/ß-endorphin pathway in antinociception.

ABO blood group does not impact incidence or outcomes of surgery for acute type A aortic dissection.

Objectives. To evaluate the distribution and impact of ABO blood groups on postoperative outcomes in patients undergoing surgery for acute type A aortic dissection (ATAAD). Design. A total of 1144 surgical ATAAD patients from eight Nordic centres constituting the Nordic consortium for acute type A aortic dissection (NORCAAD) were analysed. Blood group O patients were compared to non-O subjects. The relative frequency of blood groups was assessed with t-distribution, modified for weighted proportions. Multivariable logistic regression was performed to identify independent predictors of 30-day mortality. Cox regression analyses were performed for assessing independent predictors of late mortality. Results. There was no significant difference in the proportions of blood group O between the study populations in the NORCAAD registry and the background population (40.6 (95% CI 37.7-43.4)% vs 39.0 (95% CI 39.0-39.0)%). ABO blood group was not associated with any significant change in risk of 30-day or late mortality, with the exception of blood group A being an independent predictor of late mortality. Prevalence of postoperative complications was similar between the ABO blood groups. Conclusions. In this large cohort of Nordic ATAAD patients, there were no associations between ABO blood group and surgical incidence or outcomes, including postoperative complications and survival.

Paediatric respiratory isolation: A challenge for a secondary care hospital! A service innovation project.

OBJECTIVE: The aim of this project was to broaden the secondary care hospital's scope of services and provide safe, effective and quality care for the patient presenting with measles. METHODS: Six Sigma DMAIC [define measure, analyze, improve, and control (DMAIC)] methodology was used in this quality improvement project. The quality project was started in October 2015 using a Gantt chart quality tool. RESULTS: The paediatric team with the support of administration of the hospital has established isolation rooms and devised a policy for the care and management of patient with airborne infection to avoid cross transmission. During six months period after establishment of isolation room there were sixty two suspected or confirmed measles cases who were admitted in our hospital, out of them only 4(6.4%) of patients were referred because of their sick condition and need of ventilator support. Further, the percentage of patient's satisfaction level also improved from 60 to 80%. CONCLUSIONS: After this clinical service innovation, there was significant reduction in referrals of measles patients to another hospital and consequently there was an increase in the patient's satisfaction.

Phytochemical, antimicrobial and time-kill kinetics potentials of Euphorbia nivulia Buch.-Ham.: A Cholistan desert medicinal plant.

Euphorbia nivulia a locally occurring plant species possesses antiseptic, analgesic and anti-inflammatory properties and is ethnopharmacologically used in various ailments like skin, ear disorders, boils, and worm infestation. Preliminary phytochemical screening showed presence of flavonoids, polyphenolics, glycosides, alkaloids, tannins and triterpenoids in (70% aqueous-ethanolic) Euphorbia nivulia crude extract (En cr) and its four fractions, i.e., hexane fraction (En hex), butanol fraction (En bt), chloroform fraction (En ch), and aqueous fraction (En aq). In current study, Agar well diffusion and time-kill kinetic assays were performed for antimicrobial activity. 300 mg/ml concentration showed maximum inhibitory zone. Highest zone of inhibition (15.5mm) was demonstrated by En ch fraction against Proteus mirabilis. Staphyllococcus aureus was the most sensitive bacteria against whom all fractions except En aq fraction were active. Maximum MIC (15.3 mg/ml) was shown by En ch fraction against Proteus mirabilis. Similarly, En ch fraction showed (15.1 mg/ml) remarkable MIC against Candida albicans. Significant higher antibacterial and antifungal activity was revealed in high concentration. Time-kill kinetics studies revealed bacteriostatic action. Noteworthy antimicrobial activity may be due to bioactive compounds of extract which may be a potential antibacterial and antifungal agent.

Densely substituted piperidines as a new class of elastase inhibitors: Synthesis and molecular modeling studies.

Elastase is the only enzyme that has the capability to degrade elastin and collagen, the two proteins essential for skin and bones. The synthesis of some densely substituted piperidines functionalized with the trifluoromethyl group (4a-j) was carried out. The newly prepared compounds were subjected to elastase enzyme inhibitory potential and antioxidant activity assays. Among the series, 4i (IC50 = 0.341 ± 0.001 µM) exhibited the maximum inhibition against elastase. Binding analysis delineated that the fluorine atom of ligand 4i showed hydrogen and hydrophobic bonds with Thr41 and Thr96, with bond distances of 3.84 and 5.631 Å, respectively. The obtained results indicate that these trifluoromethyl functionalized piperidine derivatives could be considered as potential candidates to treat skin disorders.

Antiviral potential of medicinal plants against HIV, HSV, influenza, hepatitis, and coxsackievirus: A systematic review.

Viral infections are being managed therapeutically through available antiviral regimens with unsatisfactory clinical outcomes. The refractory viral infections resistant to available antiviral drugs are alarming threats and a serious health concern. For viral hepatitis, the interferon and vaccine therapies solely are not ultimate solutions due to recurrence of hepatitis C virus. Owing to the growing incidences of viral infections and especially of resistant viral strains, the available therapeutic modalities need to be improved, complemented with the discovery of novel antiviral agents to combat refractory viral infections. It is widely accepted that medicinal plant heritage is nature gifted, precious, and fueled with the valuable resources for treatment of metabolic and infectious disorders. The aims of this review are to assemble the facts and to conclude the therapeutic potential of medicinal plants in the eradication and management of various viral diseases such as influenza, human immunodeficiency virus (HIV), herpes simplex virus (HSV), hepatitis, and coxsackievirus infections, which have been proven in diverse clinical studies. The articles, published in the English language since 1982 to 2017, were included from Web of Science, Cochrane Library, AMED, CISCOM, EMBASE, MEDLINE, Scopus, and PubMed by using relevant keywords including plants possessing antiviral activity, the antiviral effects of plants, and plants used in viral disorders. The scientific literature mainly focusing on plant extracts and herbal products with therapeutic efficacies against experimental models of influenza, HIV, HSV, hepatitis, and coxsackievirus were included in the study. Pure compounds possessing antiviral activity were excluded, and plants possessing activity against viruses other than viruses in inclusion criteria were excluded. Hundreds of plant extracts with antiviral effect were recognized. However, the data from only 36 families investigated through in vitro and in vivo studies met the inclusion criteria of this review. The inferences from scientific literature review, focusing on potential therapeutic consequences of medicinal plants on experimental models of HIV, HSV, influenza, hepatitis, and coxsackievirus have ascertained the curative antiviral potential of plants. Fifty-four medicinal plants belonging to 36 different families having antiviral potential were documented. Out of 54 plants, 27 individually belong to particular plant families. On the basis of the work of several independent research groups, the therapeutic potential of medicinal plants against listed common viral diseases in the region has been proclaimed. In this context, the herbal formulations as alternative medicine may contribute to the eradication of complicated viral infection significantly. The current review consolidates the data of the various medicinal plants, those are Sambucus nigra, Caesalpinia pulcherrima, and Hypericum connatum, holding promising specific antiviral activities scientifically proven through studies on experimental animal models. Consequently, the original research addressing the development of novel nutraceuticals based on listed medicinal plants is highly recommended for the management of viral disorders.

Bilateral spontaneous anterior shoulder dislocation: A missed orthopedic injury mistaken as proximal neuropathy.

A number of orthopedic injuries can occur during epileptic seizures. Anterior shoulder dislocation is one such orthopedic injury that is quite rare. The shoulder dislocation may injure the brachial plexus. Besides seizures, the nerves can also be damaged by anticonvulsive therapy. Muscle wasting following a seizure can misguide a clinician to investigate only neural or muscular pathologies. We report here an individual with epilepsy who was referred to us for electrodiagnostic evaluation of proximal muscle wasting related to a suspected proximal neuropathy. He was found to have a normal electrodiagnostic evaluation and later on discovered to have had bilateral shoulder dislocation on X-rays. This report advocates a thorough clinical appraisal, radiographs, and electrodiagnostic evaluation in a case with muscle wasting following a seizure.

5-Lipoxygenase is a direct p53 target gene in humans.

The p53 tumor suppressor plays a critical role in cancer, and more than 50% of human tumors contain mutations or deletions of the TP53 gene. p53 can transactivate or repress target genes in response to diverse stress signals, such as transient growth arrest, DNA repair, cellular differentiation, senescence and apoptosis. Through an unbiased genome-wide ChIP-seq analysis, we have found that 5-lipoxygenase (ALOX5, 5-LO) which is a key enzyme of leukotriene (LT) biosynthesis, is a direct target gene of p53 and its expression is induced by genotoxic stress via actinomycin D (Act.D) or etoposide (Eto) treatment. 5-LO and LTs play a role in immunological diseases as well as in tumorigenesis and tumor growth. p53 binds to a specific binding site consisting of a complete p53 consensus-binding motif in ALOX5 intron G which is located about 64kbp downstream of the transcriptional start site. We confirmed the strong binding of p53 to the 5-LO target site in ChIP-qPCR experiments. Expression analyses by qRT-PCR and immunoblot further revealed that genotoxic stress induces the ALOX5 mRNA and protein expression in a p53-dependent manner. Knockdown of p53 in U2OS cells leads to a downregulation of 5-LO mRNA and protein expression. In addition, immunofluorescence and immunoprecipitation assays indicate the direct binding of 5-LO to p53 protein. Furthermore, we found that 5-LO can inhibit the transcriptional activity of p53 suggesting that 5-LO acts in a negative feedback loop to limit induction of p53 target genes.