IL4I1 Is a Metabolic Immune Checkpoint that Activates the AHR and Promotes Tumor Progression.

Aryl hydrocarbon receptor (AHR) activation by tryptophan (Trp) catabolites enhances tumor malignancy and suppresses anti-tumor immunity. The context specificity of AHR target genes has so far impeded systematic investigation of AHR activity and its upstream enzymes across human cancers. A pan-tissue AHR signature, derived by natural language processing, revealed that across 32 tumor entities, interleukin-4-induced-1 (IL4I1) associates more frequently with AHR activity than IDO1 or TDO2, hitherto recognized as the main Trp-catabolic enzymes. IL4I1 activates the AHR through the generation of indole metabolites and kynurenic acid. It associates with reduced survival in glioma patients, promotes cancer cell motility, and suppresses adaptive immunity, thereby enhancing the progression of chronic lymphocytic leukemia (CLL) in mice. Immune checkpoint blockade (ICB) induces IDO1 and IL4I1. As IDO1 inhibitors do not block IL4I1, IL4I1 may explain the failure of clinical studies combining ICB with IDO1 inhibition. Taken together, IL4I1 blockade opens new avenues for cancer therapy.

Assembly of In-Situ Gel Containing Nano-Spanlastics of an Angiotensin II Inhibitor as a Novel Epitome for Hypertension Management: Factorial Design Optimization, In-vitro Gauging, Pharmacokinetics, and Pharmacodynamics Appraisal.

More than 1 billion people worldwide suffer from hypertension; therefore, hypertension management has been categorized as a global health priority. Losartan potassium (LP) is an antihypertensive drug with a limited oral bioavailability of about 33% since it undergoes the initial metabolic cycle. Thus, nasal administration is a unique route to overcome first-pass metabolism. The investigation focused on the potential effects of LP-loaded spanlastic vesicles (SNVs) on LP pharmacodynamics and pharmacokinetic parameters, utilizing a thin-film hydration methodology established on a 3122 full factorial design. Entrapment efficiency (EE%) ranged from 39.8 ± 3.87.8 to 83.8 ± 2.92% for LP-SNVs. Vesicle size (VS) varied from 205.5 ± 6.5.10 to 445.1 ± 13.52 nm, and the percentage of LP released after 8 h (Q8h) ranged from 30.8 ± 3.10 to 68.8 ± 1.45%. LP permeated through the nasal mucosa during 24 h and flocculated from 194.1 ± 4.90 to 435.3 ± 13.53 µg/cm2. After twenty-four hours, the optimal LP-SNVs in-situ gel showed 2.35 times more permeation through the nasal mucosa than the LP solution. It also lowered systolic blood pressure, so it is thought to be better than the reference formulation in terms of pharmacodynamics. The pharmacokinetics studies demonstrated that the intranasal LP-SNVs gel boosted its bioavailability approximately 6.36 times compared to the oral LP solution. Our research showed that intranasal LP-SNVs could be a good nanoplatform because they are well-tolerated and have possible pharmacokinetics and pharmacodynamics.

Elevation of D-dimer levels are associated with early need for mechanical ventilation support in patients with COVID-19.

BACKGROUND: Severe COVID-19 disease is typically associated with an urgent need for supplemental oxygen therapy that may be successfully delivered through conventional methods or require invasive mechanical ventilation. Early prediction of the need for invasive mechanical ventilation could significantly improve outcomes of COVID-19 patients. Plasma levels of D-dimer and a number of inflammatory markers as well as values of complete blood counts, all measured in the first two days of hospital admission of COVID-19 patients, were evaluated for their significance as predictors of the eventual need for invasive mechanical ventilation support as well as their values as predictors of post-ventilation morbidly and mortality. METHODS: This retrospective cohort study was conducted at a single center and included data pertaining to 200 patients with previously confirmed moderate to severe COVID-19 disease in the period between May 2021 and the end of December 2022. Data were retrieved from medical records for further analysis. RESULTS: The mean (SD) age of patients stood at 59 (14) years of age, and with a majority of patients being male (77%). About 18% of cases, all of significantly older age, had been connected to invasive mechanical ventilation (IMV). Total leucocytic count (TLC), as well as levels of urea, creatinine, D-dimer, ferritin, and CRP in IMV patients were significantly higher than non-ventilated patients (p < 0.01 for all). In contrast, lymphocytic count, hemoglobin level, and platelet count were significantly lower in IMV patients (p < 0.001, 0.04, and 0.002, respectively). The mortality rate was significantly higher in IMV patients (p < 0.001). D-dimer independently predicted IMV demand (OR = 1, p = 0.001 in adjusted and unadjusted models). The utility of D-dimer was excellent; and the cutoff level of above 1415 µ/L showed sensitivity and specificity of about 92% and 76%, respectively. Also, the D-dimer level was very effective in predicting post-IMV survival; the AUC = 0.86, p = 0.02, and a cutoff value below 4558 µ/L was associated with 100% and 66% sensitivity and specificity, respectively. CONCLUSIONS: High D-dimer levels independently correlated with the need for invasive mechanical ventilation. Low levels of this marker could evidently predict post-IMV survival of mechanically ventilated COVID-19 patients. Measuring D-dimer levels during routine follow up of those patients would thus be useful in predicting patient outcomes.

Chitosan Schiff base electrospun fabrication and molecular docking assessment for nonleaching antibacterial nanocomposite production.

In this work, new chitosan derivative nanofibers that exhibit antibacterial properties were successfully fabricated. The two CS Schiff base derivatives (CS-APC and CS-2APC) were prepared by incorporating 4-amino antipyrine moiety in two different ratios, followed by a reductive amination to obtain the corresponding derivatives CS-APCR and CS-2APCR. Spectral analyses were used to confirm the chemical structure. The molecular docking evaluation of CS-APC, CS-APCR, and CS was conducted on DNA topoisomerase IV, thymidylate kinase and SARS-CoV-2 main protease (3CLpro) active sites. CS-APCR showed a well-fitting into the three enzyme active sites with docking score values of - 32.76, - 35.43 and - 30.12 kcal/mol, respectively. The nanocomposites of CS derivatives were obtained by electrospinning the blends of CS-2APC and CS-2APCR with polyvinyl pyrrolidone (PVP) at 20 kV. The morphology of the nanofibers was investigated by scanning electron microscopy (SEM). It was found that fiber diameters were significantly decreased when CS-2APC and CS-2APCR were incorporated into pure PVP to reach 206-296 nm and 146-170 nm, respectively, compared to 224-332 nm for pure PVP. The derivatives of CS and their nanofibers with PVP were found to have antibacterial activities against two strains of Staphylococcus aureus and Escherichia coli. Data revealed that CS-2APC nanofibers showed antibacterial activity to the two strains of E. coli less than CS-2APCR nanofibers.

Structure Activity Relationship and Molecular Docking of Some Quinazolines Bearing Sulfamerazine Moiety as New 3CLpro, cPLA2, sPLA2 Inhibitors.

The current work was conducted to synthesize several novel anti-inflammatory quinazolines having sulfamerazine moieties as new 3CLpro, cPLA2, and sPLA2 inhibitors. The thioureido derivative 3 was formed when compound 2 was treated with sulfamerazine. Also, compound 3 was reacted with NH2-NH2 in ethanol to produce the N-aminoquinazoline derivative. Additionally, derivative 4 was reacted with 4-hydroxy-3-methoxybenzaldehyde, ethyl chloroacetate, and/or diethyl oxalate to produce quinazoline derivatives 5, 6, and 12, respectively. The results of the pharmacological study indicated that the synthesized 4-6 and 12 derivatives showed good 3CLpro, cPLA2, and sPLA2 inhibitory activity. The IC50 values of the target compounds 4-6, and 12 against the SARS-CoV-2 main protease were 2.012, 3.68, 1.18, and 5.47 µM, respectively, whereas those of baicalein and ivermectin were 1.72 and 42.39 µM, respectively. The IC50 values of the target compounds 4-6, and 12 against sPLA2 were 2.84, 2.73, 1.016, and 4.45 µM, respectively, whereas those of baicalein and ivermectin were 0.89 and 109.6 µM, respectively. The IC50 values of the target compounds 4-6, and 12 against cPLA2 were 1.44, 2.08, 0.5, and 2.39 µM, respectively, whereas those of baicalein and ivermectin were 3.88 and 138.0 µM, respectively. Also, incubation of lung cells with LPS plus derivatives 4-6, and 12 caused a significant decrease in levels of sPLA2, cPLA2, IL-8, TNF-α, and NO. The inhibitory activity of the synthesized compounds was more pronounced compared to baicalein and ivermectin. In contrast to ivermectin and baicalein, bioinformatics investigations were carried out to establish the possible binding interactions between the newly synthesized compounds 2-6 and 12 and the active site of 3CLpro. Docking simulations were utilized to identify the binding affinity and binding mode of compounds 2-6 and 12 with the active sites of 3CLpro, sPLA2, and cPLA2 enzymes. Our findings demonstrated that all compounds had outstanding binding affinities, especially with the key amino acids of the target enzymes. These findings imply that compound 6 is a potential lead for the development of more effective SARS-CoV-2 Mpro inhibitors and anti-COVID-19 quinazoline derivative-based drugs. Compound 6 was shown to have more antiviral activity than baicalein and against 3CLpro. Furthermore, the IC50 value of ivermectin against the SARS-CoV-2 main protease was revealed to be 42.39 µM, indicating that it has low effectiveness.

Impacts of polyphenols on laying hens' productivity and egg quality: A review.

There has been a rapid increase in the world's output of main poultry products (meat and eggs). This reflects customer desire for these high-quality and safe products and the comparatively low price. Recently, natural feed additives, plants and products have been increasingly popular in the poultry and livestock industries to maintain and improve their health and production. Polyphenols are a type of micronutrient that is plentiful in our diet. They are phytochemicals that have health benefits, notably cardiovascular, cognitive function, antioxidant, anti-mutagenic, anti-inflammatory, antistress, anti-tumour, anti-pathogen, detoxification, growth-promoting and immunomodulating activities. On the other hand, excessive polyphenol levels have an unclear and sometimes negative impact on gastrointestinal tract health, nutrient digestion, digestive enzyme activity, vitamin, mineral absorption, laying hens performance and egg quality. As a result, this review illuminated polyphenols' various sources, classifications, biological activities, potential usage restrictions and effects on poultry, layer productivity and egg external and internal quality.

Clinical Care Team's Guide for Awareness on Risk Assessment of Eltrombopag Complicating Acute Kidney Injury in Relapsed Immune Thrombocytopenic Patients: A Case Report.

Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder caused by antigen-specific T cells and antiplatelet autoantibodies that inhibit platelet production in the bone marrow or destroy platelets in the spleen. ITP is a form of autoimmunity and is closely associated with inflammation. Corticosteroids are the first-line therapy for ITP, with a total response rate of 53-80%. However, corticosteroid therapy is associated with significant side effects and is often ineffective in patients with corticosteroid-resistant or -intolerant disease. Eltrombopag has been validated as a second-line option in ITP therapy. Despite several studies demonstrating the efficacy and safety of Eltrombopag in immune thrombocytopenia patients, the prevalence of Eltrombopag-induced acute kidney injury has been observed. This case report describes a patient who experienced acute kidney injury during Eltrombopag therapy. A sudden increase in serum creatinine to 6.7 mg/dL and metabolic acidosis occurred after eight weeks of Eltrombopag. The patient's renal failure had worsened, proteinuria was detected, and emergency hemodialysis was initiated. With vigilant kidney function screening and prompt treatment, the patient's renal function improved remarkably following cessation of Eltrombopag and initiation of hemodialysis. This case highlights the importance of comprehensive medication history-taking and vigilant kidney function screening in patients receiving Eltrombopag.

Chronotherapeutic neuroprotective effect of verapamil against lipopolysaccharide-induced neuroinflammation in mice through modulation of calcium-dependent genes.

BACKGROUND: Neuroinflammation is a major mechanism in neurodegenerative diseases such as Alzheimer's disease (AD), which is a major healthcare problem. Notwithstanding of ample researches figured out possible molecular mechanisms underlying the pathophysiology of AD, there is no definitive therapeutics that aid in neuroprotection. Therefore, searching for new agents and potential targets is a critical demand. We aimed to investigate the neuroprotective effect of verapamil (VRP) against lipopolysaccharide (LPS)-induced neuroinflammation in mice and whether the time of VRP administration could affect its efficacy. METHODS: Forty male albino mice were used and were divided into normal control, LPS only, morning VRP, and evening VRP. Y-maze and pole climbing test were performed as behavioral tests. Hematoxylin and eosin together with Bielschowsky silver staining were done to visualize neuroinflammation and phosphorylated tau protein (pTAU); respectively. Additionally, the state of mitochondria, the levels of microglia-activation markers, inflammatory cytokines, intracellular Ca2+, pTAU, and Ca2+-dependent genes involving Ca2+/ calmodulin dependent kinase II (CAMKII) isoforms, protein kinase A (PKA), cAMP response element-binding protein (CREB), and brain-derived neurotrophic factor (BDNF), with the level of VRP in the brain tissue were measured. RESULTS: LPS successfully induced neuroinflammation and hyperphosphorylation of tau protein, which was indicated by elevated levels of microglia markers, inflammatory cytokines, and intracellular Ca2+ with compromised mitochondria and downregulated CAMKII isoforms, PKA, CREB and BDNF. Pretreatment with VRP showed significant enhancement in the architecture of the brain and in the behavioral tests as indicated by the measured parameters. Moreover, morning VRP exhibited better neuroprotective profile compared to the evening therapy. CONCLUSIONS: VRP highlighted a multilevel of neuroprotection through anti-inflammatory activity, Ca2+ blockage, and regulation of Ca2+-dependent genes. Furthermore, chronotherapy of VRP administration should be consider to achieve best therapeutic efficacy.

Naringenin affords protection against lipopolysaccharide/D-galactosamine-induced acute liver failure: Role of autophagy.

Acute liver failure (ALF) is considered a fatal clinical disorder and novel therapeutic interventions are mandatory. Naringenin is a flavonoid with anti-inflammatory, antioxidant and antiapoptotic effects that have displayed beneficial effects in different animal models of ALF. The current study aimed at investigating the hepatoprotective effect and the possible underlying molecular mechanisms of naringenin in lipopolysaccharide (LPS)/D-galactosamine (D-Gal) mouse model of ALF. Interestingly, naringenin pretreatment substantially alleviated LPS/D-Gal-induced liver injury, enhanced survival, improved liver function and ameliorated histopathological liver changes. Importantly, naringenin potently activated autophagy as evidenced by the increased Beclin-1 expression and LC3 II/LC3 I ratio. Furthermore, results demonstrated that naringenin alleviated oxidative stress by inducing nuclear factor-erythroid 2-related factor 2 (Nrf2) and increasing hepatic SOD activity and GSH level as well as ameliorated endoplasmic reticulum (ER) stress. Likewise, naringenin mitigated LPS/D-Gal-triggered inflammation by suppressing NF-κB and NLRP3 pathways. Accordingly, apoptotic cell death provoked by LPS/D-Gal challenge was markedly attenuated as depicted by the decrease in caspase-3 and p53 in naringenin-treated mice. To investigate the contribution of autophagy to naringenin-conferred hepatoprotection, autophagy was inhibited using 3-methyladenine (3 MA). Strikingly, 3 MA co-treatment abolished the hepatoprotective effect of naringenin, a finding that strongly suggests that naringenin-afforded protection is, at least in part, attributed to autophagy. Taken together, the present study revealed that naringenin exerted a prominent hepatoprotective effect by promoting autophagy with consequent attenuation of inflammatory responses, oxidative stress, ER stress and apoptosis. Our results provide evidence that naringenin use holds a promise as a potential therapeutic agent for ALF management.

Effect of environmental factors on growth performance of Nile tilapia (Oreochromis niloticus).

Aquaculture is the practice of developing aquatic animals and plants under artificial environmental conditions, either in a controlled or semi-controlled environment. Due to high animal protein demand, it is one of the world's growing food production industries. It plays a vital role in contributing to food security and lowering the unemployment rate of the world's growing population. This review article aims to scope sight on the environmental factors that affect the growth and economic production process of Nile tilapia. Many of these factors are listed and analyzed in this review, such as stocking densities; various feed frequencies and feeding rates; water quality; water temperature; dissolved oxygen concentration; water pH degree; ammonia (NH3), nitrite (NO2), and nitrate (NO3) concentration; feeding regimes; feed cost; and tank culturing system of Nile tilapia. These factors can significantly alter body weight, composition, survival, behavior, feed intake, feed conversion ratio, feeding efficiency, and the health and reproduction of Oreochromis niloticus. Furthermore, feeding, growth, disease risks, and survival rates are all affected by water quality parameters. In general, higher growth performance of O. niloticus in aquaculture can be obtained by keeping the optimum quantity of feed with proper feeding rate and frequency, maintaining a good proportion of stocking density, and regularly evaluating water quality. This review article highlights-in details-the impact of various environmental factors on growth performance criteria of Nile tilapia (Oreochromis niloticus).

Rosuvastatin calcium-based novel nanocubic vesicles capped with silver nanoparticles-loaded hydrogel for wound healing management: optimization employing Box-Behnken design: in vitro and in vivo assessment.

Chronic wounds are a serious problem that could cause severe morbidity and even death. The ability of statins including rosuvastatin calcium (RVS) to enhance wound healing was well reported. However, RVS is poorly soluble and has low bioavailability. Thus, this study aimed to prepare and evaluate RVS-loaded nanocubics to enhance its skin performance. In addition, silver nanoparticles (AgNPs) exhibited potent antimicrobial activity, thus, the optimum RVS-loaded nanocubics was capped with AgNPs to evaluate its effect in wound management. Box-Behnken design was adopted to prepare RVS nanocubics. The design investigated the effect of lecithin, poloxamer 407 concentrations and hydration time on vesicle size, zeta potential (ZP), entrapment efficiency (EE%) and in vitro drug release%. Optimum formulation capped with AgNPs was incorporated into a gel base and examined for wound healing efficiency using different pharmacological tests in rats. Nanocubics have shown a mean diameter between 167.2 ± 7.8 and 408 ± 18.4 nm, ZP values ranging from -20.9 ± 1.9 to -53.5 ± 4 mV, EE% equivocated between 31.6 ± 1.4 and 94.4 ± 8.6 and drug release after 12 h between 17.9 ± 1.9 and 68.0 ± 4.0%. The histopathological studies and serum tumour necrosis factor alpha (TNF-α) and interleukin-1ß (IL-1ß) levels confirmed the greater efficacy of RVS nanocubics capped with AgNPs gel in wound healing when compared with gentamicin ointment. RVS-loaded nanocubic vesicles and AgNPs-loaded hydrogel could be considered as a promising platform to enhance the wound healing and tissue repair processes.

Heat stress in poultry with particular reference to the role of probiotics in its amelioration: An updated review.

Global climate change is accelerating at an unprecedented rate, and the consequences of global warming are expected to worsen. Many heat waves have recently hit various parts of the world, causing major losses in livestock, particularly in the poultry sector, resulting in massive mortalities and catastrophic economic losses. Therefore, the current review sheds light on the effects of heat stress on the poultry industry, and discusses the factors relevant to these harmful effects on behavior, bone development, blood chemistry and physiological changes, pathogenesis, and immune responses. Potential methods to ameliorate the heat stress response in birds, with particular reference to the role of probiotics in controlling such problems, is further discussed.

Betaine and related compounds: Chemistry, metabolism and role in mitigating heat stress in poultry.

Betaine can operate as an osmolyte and a methyl donor. Betaine is an osmolyte and a methyl donor. Betaine is likewise a zwitterion with osmotic capabilities that can help an animal cope with osmotic stress. Previous investigations have suggested that betaine has various impacts, albeit these studies do not consistently provide the same results. Dietary betaine has received a lot of attention owing to its osmoprotectant, methionine-sparing and antioxidant properties. Betaine is extensively assessed concerning performance and body composition. The tolerance to high temperatures, flock livability, and breast meat output is among the factors frequently mentioned in the literature as being altered by betaine. Betaine, a multi-nutritional agent, may help poultry resist heat stress and poor management. A common subject of betaine research is the idea of betaine saving some methionine. Although research on betaine may not always come to the same results, some discoveries repeat themselves. Because of their effectiveness in increasing growth performance, feed utilization, meat quality, and alleviating heat stress in chicken farms, betaine and methionine are extensively used as feed supplements in poultry diets. This review highlights the influences of betaine on poultry performance, meat quality, carcass characteristics, antioxidant activity, in addition to its role in mitigating heat stress.

Potential Mechanisms Involved in the Protective Effect of Dicaffeoylquinic Acids from Artemisia annua L. Leaves against Diabetes and Its Complications.

Diabetes mellitus is a chronic disease affecting the globe and its incidence is increasing pandemically. The use of plant-derived natural products for diabetes management is of great interest. Polar fraction of Artemisia annua L. leaves has shown antidiabetic activity in vivo. In the present study, three major compounds were isolated from this polar fraction; namely, 3,5-dicaffeoylquinic acid (1); 4,5-dicaffeoylquinic acid (2), and 3,4- dicaffeoylquinic acid methyl ester (3), using VLC-RP-18 and HPLC techniques. The potential protective effects of these compounds against diabetes and its complications were investigated by employing various in vitro enzyme inhibition assays. Furthermore, their antioxidant and wound healing effectiveness were evaluated. Results declared that these dicaffeoylquinic acids greatly inhibited DPPIV enzyme while moderately inhibited α-glucosidase enzyme, where compounds 1 and 3 displayed the most prominent effects. In addition, compound 3 showed pronounced inhibition of α-amylase enzyme. Moreover, these compounds markedly inhibited aldose reductase enzyme and exerted powerful antioxidant effects, among which compound 3 exhibited the highest activity implying a notable potentiality in impeding diabetes complications. Interestingly, compounds 2 and 3 moderately accelerated scratch wound healing. Our findings suggest that these dicaffeoylquinic acids can be promising therapeutic agents for managing diabetes and its complications.

Development and Greenness Assessment of HPLC Method for Studying the Pharmacokinetics of Co-Administered Metformin and Papaya Extract.

Foods with medical value have been proven to be beneficial, and they are extensively employed since they integrate two essential elements: food and medication. Accordingly, diabetic patients can benefit from papaya because the fruit is low in sugar and high in antioxidants. An RP-HPLC method was designed for studying the pharmacokinetics of metformin (MET) when concurrently administered with papaya extract. A mobile phase of 0.5 mM of KH2PO4 solution and methanol (65:35, v/v), pH = 5 ± 0.2 using aqueous phosphoric acid and NaOH, and guaifenesin (GUF) were used as an internal standard. To perform non-compartmental pharmacokinetic analysis, the Pharmacokinetic program (PK Solver) was used. The method's greenness was analyzed using two tools: the Analytical GREEnness calculator and the RGB additive color model. Taking papaya with MET improved the rate of absorption substantially (time for reaching maximum concentration (Tmax) significantly decreased by 75% while maximum plasma concentration (Cmax) increased by 7.33%). The extent of absorption reduced by 22.90%. Furthermore, the amount of medication distributed increased (30.83 L for MET concurrently used with papaya extract versus 24.25 L for MET used alone) and the clearance rate rose by roughly 13.50%. The results of the greenness assessment indicated that the method is environmentally friendly. Taking papaya with MET changed the pharmacokinetics of the drug dramatically. Hence, this combination will be particularly effective in maintaining quick blood glucose control.

Emergence of High Antimicrobial Resistance among Critically Ill Patients with Hospital-Acquired Infections in a Tertiary Care Hospital.

Background and Objectives: Inappropriate antibiotic usage in hospitalized patients contributes to microbial resistance. Our study aimed to examine the incidence of clinical bacterial isolates and their antibiotic resistance burden among critically ill patients in different hospital units. Materials and Methods: A single-centered cross-sectional study was conducted in a 120-bed tertiary care hospital that included 221 critically ill patients with hospital-acquired infections. Bacterial cultures and sensitivity reports were obtained and followed by a formal analysis of the antibiogram results to explore recovered isolates' prevalence and antibiotic susceptibility patterns. Results: Gram-negative bacteria were the most predominant pathogens among recovered isolates from the various hospital units (71%). Klebsiella sp. was the most prevalent microbe, followed by Acinetobacter sp., with an incidence level of 28% and 16.2%, respectively. Among the Gram-positive organisms, the coagulase-negative Staphylococci were the most predominant organism (11.3%), while (6.3%) methicillin-resistant Staphylococcus aureus (MRSA) isolates were recovered from different hospital units. Antibiotic sensitivity testing showed that polymyxin B was the most effective antibiotic against Gram-negative bacteria, whereas vancomycin and linezolid were the most active antibiotics against Gram-positive pathogens. Moreover, 7% of the Gram-negative bacteria isolated from different units showed positive production of extended-spectrum beta-lactamase (ESBL). Conclusions: The current study describes the high antibiotic resistance patterns in various hospital units that need extra legislation to prevent healthcare providers from misprescription and overuse of antibiotics.

Prevalence and Survival of Stenotrophomonas Species in Milk and Dairy Products in Egypt.

Stenotrophomonas maltophilia is a nosocomial, multidrug-resistant pathogen that causes significant economic losses in milk production and deterioration of dairy product quality. This study investigates the prevalence and the survival of S. maltophilia under different food preservation conditions. A total of 240 samples, including farm-sourced milk, dairy shop purchased milk, Kareish cheese, Domiati cheese, ice cream, yoghurt, cooking butter, and unpasteurized cream were collected from various locations in Beni-Suef Governorate, Egypt. Thirty samples of each product were analyzed by standard biochemical tests for the presence of Stenotrophomonas spp., which was isolated from 36% (87/240) of the examined samples. The highest prevalence was observed in ice cream (80%), followed by unpasteurized cream (67%), whereas the lowest incidence was in Domiati cheese (3.3%). S. maltophilia, identified by PCR, was found only in unpasteurized cream (13%), cooking butter (10%), ice cream (6.7%), and dairy shop milk (3.3%). We also studied the viability of S. maltophilia in laboratory manufactured cream, butter, and cheese under different preservation conditions. S. maltophilia was able to survive for 30, 30, 28, 30, and 8 d in the inoculated cream, butter 0% salt, butter 3% salt, cheese 0% salt, and cheese 6% salt, respectively. Thus, S. maltophilia was able to survive more than predicted in all products in this study. This suggests that strains of S. maltophilia may develop adaptive strategies that enable survival under different food preservation conditions, which contradicts previous knowledge about the sensitivity of this microbe to environmental stress conditions. Our overall aim was to draw attention to the prevalence and future potential for increased public health significance of Stenotrophomonas spp.

Treadmill Exercise Training Ameliorates Functional and Structural Age-Associated Kidney Changes in Male Albino Rats.

Aging is a biological process that impacts multiple organs. Unfortunately, kidney aging affects the quality of life with high mortality rate. So, searching for innovative nonpharmacological modality improving age-associated kidney deterioration is important. This study aimed to throw more light on the beneficial effect of treadmill exercise on the aged kidney. Thirty male albino rats were divided into three groups: young (3-4 months old), sedentary aged (23-24 months old), and exercised aged (23-24 months old, practiced moderate-intensity treadmill exercise 5 days/week for 8 weeks). The results showed marked structural alterations in the aged kidney with concomitant impairment of kidney functions and increase in arterial blood pressure with no significant difference in kidney weight. Also, it revealed that treadmill exercise alleviated theses effects in exercised aged group with reduction of urea and cystatin C. Exercise training significantly decreased glomerulosclerosis index, tubular injury score, and % area of collagen deposition. Treadmill exercise exerted its beneficial role via a significant reduction of C-reactive protein and malondialdehyde and increase in total antioxidant capacity. In addition, exercise training significantly decreased desmin immunoreaction and increased aquaporin-3, vascular endothelial growth factor, and beclin-1 in the aged kidney. This study clarified that treadmill exercise exerted its effects via antioxidant and anti-inflammatory mechanisms, podocyte protection, improving aquaporin-3 and vascular endothelial growth factor expression, and inducing autophagy in the aged kidney. This work provided a new insight into the promising role of aerobic exercise to ameliorate age-associated kidney damage.

Synthesis, Molecular Docking, and Biofilm Formation Inhibitory Activity of Bis(Indolyl)Pyridines Analogues of the Marine Alkaloid Nortopsentin.

An efficient and simple protocol for the synthesis of a new class of diverse bis(indolyl)pyridines analogues of the marine alkaloid nortopsentin has been reported. A one-pot four-component condensation of 3-cyanocarbomethylindole, various aldehyde, 3-acetylindole, and ammonium acetate in glacial acetic acid led to the formation of 2,6-bis(1H-indol-3-yl)-4-(substituted-phenyl)pyridine-5-carbonitriles. Additionally, 2,6-bis(1H-indol-3-yl)-4-(benzofuran) pyridine-5-carbonitriles were prepared via a one-pot four-component condensation of 3-cyanocarbomethylindole, various N-substituted-indole-3-aldehydes, 2-acetylbenzofuran, and ammonium acetate. The synthesized compounds were evaluated for their ability to inhibit biofilm formation against the Gram-positive bacterial reference strains Staphylococcus aureus ATCC 6538 and the Gram-negative strain Escherichia coli ATCC 25922. Some of the new compounds showed a marked selectivity against the Gram-positive and Gram-negative strains. Remarkably, five compounds 4b, 7a, 7c, 7d and 8e demonstrated good antibiofilm formation against S. aureus and E. coli. On the other hand, the release of reducing sugars and proteins from the treated bacterial strains over the untreated strains was considered to explain the disruption effect of the selected compound on the contact cells of S. aureus and E. coli. Out of all studied compounds, the binding energies and binding mode of bis-indole derivatives 7c and 7d were theoretically the best thymidylate kinase, DNA gyrase B and DNA topoisomerase IV subunit B inhibitors.

Treatment of breast cancer with engineered novel pH-sensitive triaryl-(Z)-olefin niosomes containing hydrogel: an in vitro and in vivo study.

Triaryl-(Z)-olefin (TZO) was synthesized as a Tamoxifen (TMX) analogue for breast cancer treatment to avoid developing the resistance and toxicity of TMX. TZO was synthesized using McMurry olefination reaction and has anti-cancer activity better than TMX by two folds. In this paper, in situ pH-sensitive TZO-loaded noisome hydrogel was prepared for delivering and targeting TZO to its site of activity. Equi-molar of cholesterol and span 60 was used to prepare TZO-loaded niosomes using the Hand Shaking Method. The central composite experimental design was used to prepare differently in situ pH-sensitive TZO-loaded niosomes formulae. The formulae were done by incorporated TZO-loaded niosomes into different concentrations of chitosan and Glyceryl monooleate (GCM). Increasing the chitosan and GCM concentrations resulted in significantly increasing the viscosity and significantly decreasing the release of TZO from different formulae. The formula composed of (0.61% w/v) of chitosan and (0.23% w/v) of GCM was chosen as an optimum formula to evaluate the efficacy of TZO using Ehrlich carcinoma mice model. A significant anti-tumour effect was shown in comparison with TMX. Briefly, in situ pH-sensitive TZO-loaded niosomes could be an effective treatment for breast cancer.