Boosting the Anti-Helicobacter Efficacy of Azithromycin through Natural Compounds: Insights From In Vitro, In Vivo, Histopathological, and Molecular Docking Investigations.

BACKGROUND: Antimicrobial-resistant Helicobacter pylori (H. pylori) poses a significant public health concern, especially given the limited therapeutic options for azithromycin-resistant strains. Hence, there is a necessity for new studies to reconsider the use of azithromycin, which has diminished in effectiveness against numerous strains. Thus, we aimed to augment azithromycin's anti-Helicobacter properties by combining it with curcumin in different formulations, including curcumin in clove oil, curcumin nano-gold emulsion, and curcumin nanoemulsion. METHODS: The antimicrobial activities of the investigated compounds, both individually and in combination with other anti-Helicobacter drugs, were evaluated. Their antibiofilm and anti-virulence properties were assessed using both phenotypic and genotypic methods, alongside molecular docking studies. Our findings were further validated through mouse protection assays and histopathological analysis. RESULTS: We observed high anti-Helicobacter activities of curcumin, especially curcumin nanoemulsion. A synergistic effect was detected between curcumin nanoemulsion and azithromycin with fraction inhibitory concentration index (FICI) values <0.5. The curcumin nanoemulsion was the most active anti-biofilm and anti-virulence compound among the examined substances. The biofilm-correlated virulence genes (babA and hopQ) and ureA genes were downregulated (fold change <1) post-treatment with curcumin nanoemulsion. On the protein level, the anti-virulence activities of curcumin nanoemulsion were documented based on molecular docking studies. These findings aligned with histopathological scoring of challenge mice, affirming the superior efficacy of curcumin nanoemulsion/azithromycin combination. CONCLUSION: The anti-Helicobacter activities of all curcumin physical forms pose significant challenges due to their higher  minimum inhibitory concentration (MIC) values exceeding the maximum permissible level. However, using curcumin nanoemulsion at sub-MIC levels could enhance the anti-Helicobacter activity of azithromycin and exhibit anti-virulence properties, thereby improving patient outcomes and addressing resistant pathogens. Therefore, more extensive studies are necessary to assess the safety of incorporating curcumin nanoemulsion into H. pylori treatment.

CAR-T cell therapeutic avenue for fighting cardiac fibrosis: Roadblocks and perspectives.

Heart diseases remain the primary cause of human mortality in the world. Although conventional therapeutic opportunities fail to halt or recover cardiac fibrosis, the promising clinical results and therapeutic efficacy of engineered chimeric antigen receptor (CAR) T cell therapy show several advancements. However, the current models of CAR-T cells need further improvement since the T cells are associated with the triggering of excessive inflammatory cytokines that directly affect cardiac functions. Thus, the current study highlights the critical function of heart immune cells in tissue fibrosis and repair. The study also confirms CAR-T cell as an emerging therapeutic for treating cardiac fibrosis, explores the current roadblocks to CAR-T cell therapy, and considers future outlooks for research development.

ABO, Lewis blood group systems and secretory status with H.pylori infection in yemeni dyspeptic patients: a cross- sectional study.

BACKGROUND: The ABO and Lewis blood group antigens are potential factors in susceptibility to H. pylori infection. This research aimed to examine the prevalence of Helicobater pylori (H.pylori) infection and its association with ABO, Lewis blood group systems, and secretory status in Yemeni symptomatic patients. METHODS: In a cross-sectional study, 103 patients referred for endoscopy due to dyspepsia were included. H pylori infection was assessed using stool antigen and serum antibody rapid tests. ABO and Lewis blood group systems were examined using hemagglutination assay. Saliva samples were investigated for identification of the secretory phenotype using hemagglutination inhibition test. RESULTS: The prevalence of H. pylori infection was (80.6%), with a higher rate of infection in females than males. The ABO blood groups were found to be significantly different between males and females (p = 0.047). The O blood group was prevalent among H. pylori patients, especially secretors. There was a significant association between ABO blood groups and H. pylori infection (p = 0.001). The Le (a + b+) phenotype was the most common, followed by Le (a + b-), Le (a-b+), and Le (a-b-). Lewis blood group systems and secretory status of symptomatic patients were not associated with H. pylori infection. The results showed that serum Ab test for H. pylori achieved poor sensitivity (68%), specificity of 55%; positive predictive value (PPV) 86%, negative predictive value (NPV) 29% and accuracy 65.1%. CONCLUSION: The prevalence of H. pylori infection was high in Yemeni patients. This infection was linked to the O and Le (a + b+) secretor phenotype. The H. pylori stool Ag test is the most reliable noninvasive diagnostic method for detecting H. pylori infection.

WRH-2412 alleviates the progression of hepatocellular carcinoma through regulation of TGF-ß/ß-catenin/α-SMA pathway.

Hepatocellular carcinoma is considered one of the most lethal cancers, which is characterised by increasing prevalence associated with high level of invasion and metastasis. The novel synthetic pyrazolo[3,4-b]pyridine compound, WRH-2412, was reported to exhibit in vitro antitumor activity. This study was conducted to evaluate the antitumor activity of WRH-2412 in HCC induced in rats through affecting the TGF-ß/ß-catenin/α-SMA pathway. Antitumor activity of WRH-2412 was evaluated by calculating the rat's survival rate and by assessment of serum α-fetoprotein. Protein expression of TGF-ß, ß-catenin, E-cadherin, fascin and gene expression of SMAD4 and α-SMA were determined in hepatic tissue of rats. WRH-2412 produced antitumor activity by significantly increasing the rats' survival rate and decreasing serum α-fetoprotein. WRH-2412 significantly reduced an HCC-induced increase in hepatic TGF-ß, ß-catenin, SMAD4, fascin and α-SMA expression. In addition, WRH-2412 significantly increased hepatic E-cadherin expression.

Therapeutic Potential of Albumin Nanoparticles Encapsulated Visnagin in MDA-MB-468 Triple-Negative Breast Cancer Cells.

Breast cancer is among the most recurrent malignancies, and its prevalence is rising. With only a few treatment options available, there is an immediate need to search for better alternatives. In this regard, nanotechnology has been applied to develop potential chemotherapeutic techniques, particularly for cancer therapy. Specifically, albumin-based nanoparticles are a developing platform for the administration of diverse chemotherapy drugs owing to their biocompatibility and non-toxicity. Visnagin, a naturally derived furanochromone, treats cancers, epilepsy, angina, coughs, and inflammatory illnesses. In the current study, the synthesis and characterization of albumin visnagin (AV) nanoparticles (NPs) using a variety of techniques such as transmission electron microscopy, UV-visible, Fourier transform infrared, energy dispersive X-ray composition analysis, field emission scanning electron microscopy, photoluminescence, X-Ray diffraction, and dynamic light scattering analyses have been carried out. The MTT test, dual AO/EB, DCFH-DA, Annexin-V-FITC/PI, Propidium iodide staining techniques as well as analysis of apoptotic proteins, antioxidant enzymes, and PI3K/Akt/mTOR signaling analysis was performed to examine the NPs' efficacy to suppress MDA-MB-468 cell lines. The NPs decreased cell viability increased the amount of ROS in the cells, disrupted membrane integrity, decreased the level of antioxidant enzymes, induced cell cycle arrest, and activated the PI3K/Akt/mTOR signaling cascade, ultimately leading to cell death. Thus, AV NPs possesses huge potential to be employed as a strong anticancer therapy alternative.

Hematological indices and abnormalities among patients with uncomplicated falciparum malaria in Kosti city of the White Nile state, Sudan: a comparative study.

BACKGROUND: Hematological abnormalities are common features in falciparum malaria but vary among different populations across countries. Therefore, we compared hematological indices and abnormalities between Plasmodium falciparum-infected patients and malaria-negative subjects in Kosti city of the White Nile State, Sudan. METHODS: A comparative, cross-sectional study was conducted at the Clinical Laboratory Unit of Kosti Teaching Hospital from June to December 2018. A total of 392 participants (192 P. falciparum-infected patients and 200 malaria-negative subjects) were recruited in the study. Hematological indices of hemoglobin (Hb), red blood cells (RBCs), white blood cells (WBCs) and platelets were measured, and their median values were statistically compared. RESULTS: The majority of P. falciparum-infected patients (67.6%) showed a low-level parasitemia. The median values of Hb concentration, RBC count, mean corpuscular volume (MCV), mean corpuscular Hb (MCH) and mean corpuscular Hb concentration (MCHC) were significantly lower in P. falciparum-infected patients, while the median red cell distribution width (RDW) was significantly higher in the patients compared to malaria-negative subjects. Anemia, low MCV, low MCH, low MCHC and high RDW were significantly associated with falciparum malaria, but parasitemia level was not significantly associated with anemia severity. The median total WBC count was non-significantly higher in P. falciparum-infected patients, with neutropenia being significantly associated with falciparum malaria. The median platelet count was significantly lower in P. falciparum-infected patients, with thrombocytopenia being significantly associated with falciparum malaria. CONCLUSIONS: Falciparum malaria among patients in Kosti city of the White Nile State, Sudan is predominantly of low-level parasitemia. It is significantly associated with anemia, low MCV, low MCH, low MCHC, high RDW, thrombocytopenia and neutropenia. However, parasitemia level is not a significant predictor of anemia severity. On the other hand, leucopenia is not useful to predict falciparum malaria. Further large-scale studies in community and healthcare settings and inclusion of patients with complicated or severe malaria and those with high parasite densities are recommended.

Artificial Neural Network as a Tool for Appraising Hematological Parameters in Sudanese Patients with Malaria.

BACKGROUND: The purpose of this paper was to quantitatively assess and explore the effect of malaria infection in the hematological parameters of Sudanese population. METHODS: All data were obtained from malaria infected and non-infected Sudanese patients attending to Kosti Teaching Hospital. The effect of malaria on the hematological parameters was depicted. The relationships between hematological parameters with the effect of malaria in the two groups were assessed using Spearman's correlation. The quantitative effects of malaria on the hematological parameters were assessed using SPSS 21.0 software with a neutral network feature. RESULTS: There was no correlation between the effect of malaria infection and MCV, PCV, and MCHC (r = 0.055, r = 0.087, and r = 0.067, respectively) among Sudanese population (p > 0.05). An obvious correlation was observed between hemoglobin concentration (Hb Conc.), RBC count, MCH, and ESR and the effect of malaria infection (r = -0.226, r = 0.285, r = 0.286, and r = -0.378, respectively (p < 0.05). The effect of malaria infection on PCV standardized percentage (100%) was much higher than other hematological parameters. CONCLUSIONS: Changes in the PCV measurements among Sudanese patients may be associated with the higher effect of malaria infection. Because malaria is caused by a blood parasite, early diagnosis and treatment could contribute to improve the individual health status.

Esophageal cancer epidemiology, diagnosis, and management in Sudan - A review.

INTRODUCTION: In Sudan, cancer a common health challenge, is the leading cause of death after malaria and viral pneumonia. The aim of the review is to determine the risk factors associated with esophageal cancer (EC) among Sudanese population. METHODS: All published online data concerning EC epidemiology, diagnosis, and management in Sudan were studied. RESULTS: The prevalence of EC in Sudan is ranked fourth among cancer types in males and fifth in females. The squamous cell carcinoma is more predominant than adenocarcinoma. The dietary, dysplasia and teeth loss, cigarette smoking, age, sex, GERD, genetic and environmental interactions remain a risk for developing EC in clinical practice. A significant challenge for treatment is that most of EC patients were often diagnosed in advanced stages due to the lack of early clinical symptoms. Management of EC depends on patient fitness and tumor stage, endoscopic removal was used for early tumors, while chemotherapy, chemo-radiotherapy, surgical resection, or combinations of these were used for advanced tumors. Despite improvements in the management and treatment of EC patients, the general outcome remains very poor. Furthermore, using molecular techniques to better understand the etiology of EC, it may assist in identifying complicated and critical issues and improve therapy towards a new treatment strategy. CONCLUSION: The remarkable factors associated with EC among Sudanese are geographical variation, environmental factors, ethnic differences, dietary and social habits.

Biopolymer-Based Microcarriers for Three-Dimensional Cell Culture and Engineered Tissue Formation.

The concept of three-dimensional (3D) cell culture has been proposed to maintain cellular morphology and function as in vivo. Among different approaches for 3D cell culture, microcarrier technology provides a promising tool for cell adhesion, proliferation, and cellular interactions in 3D space mimicking the in vivo microenvironment. In particular, microcarriers based on biopolymers have been widely investigated because of their superior biocompatibility and biodegradability. Moreover, through bottom-up assembly, microcarriers have opened a bright door for fabricating engineered tissues, which is one of the cutting-edge topics in tissue engineering and regeneration medicine. This review takes an in-depth look into the recent advancements of microcarriers based on biopolymers-especially polysaccharides such as chitosan, chitin, cellulose, hyaluronic acid, alginate, and laminarin-for 3D cell culture and the fabrication of engineered tissues based on them. The current limitations and potential strategies were also discussed to shed some light on future directions.

Wastewater degradation by iron/copper nanoparticles and the microorganism growth rate.

Nowadays, trends in wastewater treatment by zero-valent iron (ZVI) were turned to use bimetallic NZVI particles by planting another metal onto the ZVI surface to increase its reactivity. Nano size zero-valent iron/copper (NZVI/Cu0) bimetallic particles were synthesized in order to examine its toxicity effects on the wastewater microbial life, kinetics of phosphorus, ammonia stripping and the reduction of chemical oxygen demand (COD). Various concentrations of NZVI/Cu0 and operation conditions both aerobic and anaerobic were investigated and compared with pure NZVI experiment. The results showed that addition 10mg/L of NZVI/Cu0 significantly increased the numbers of bacteria colonies under anaerobic condition, conversely it inhibited bacteria activity with the presence of oxygen. Furthermore, the impact of nanoparticles on ammonia stripping and phosphorus removal was also linked to the emitted iron ions electrons. It was found that dosing high concentration of bimetallic NZVI/Cu0 has a negative effect on ammonia stripping regardless of the aeration condition. In comparison to control, dosing only 10mg/L NZVI/Cu0, the phosphorus removal increased sharply both under aerobic and anaerobic conditions, these outcomes were obtained as a result of complete dissolution of bimetallic nanoparticles which formed copper-iron oxides components that are attributed to increasing the phosphorus adsorption rate.

Primary wound closure of diabetic foot ulcers by debridement and stitching.

OBJECTIVE: The role of stitching in healing diabetic foot ulcers (DFUs) has little attention, with few reports published on the technique. This study aimed to report on the role of stitching in healing of neuropathic DFUs. METHOD: This comparative study was between patients with diabetes with neuropathic foot ulcers who had undergone wound stitching and those on conventional wound care. The study was carried in Jabir Abu Eliz Diabetic Center Khartoum (JADC) during between January 1 2011 and January 1 2013. All patients presented with neuropathic diabetic septic foot on the plantar aspect or extending up the leg were included. Initial surgical sharp debridement under intravenous broad spectrum antibiotics was performed and oral antibiotics were given 3 days later after the results of the bacterial culture were received. Regular wound debridement was performed with the aim of pairing the wound edges for stitching. Primary closure was performed when the wound was clean from any necrotic tissues and partial closure when the wound was still oozy to secure drainage and avoid splaying of the wound edges. All patients were using either crutches or wheel chair initially until any sepsis cleared and then proper off-loading by shoes purpose made in our centre. RESULTS: A 160 patients with neuropathic DFUs that needed debridement and frequent dressing changes as outpatients were included. Both groups had the same tap water wound dressing either daily, every other day or every two days according to the wound progress. Absorbent dressings and negative pressure wound therapy (NPWT) were unavailable. Half of the patients (n=80) had debridement, frequent dressing change using tap water throughout the period of study (group 1) while the rest (n=80) in addition to wound debridement underwent stitching of their wounds (group 2). Complete healing was achieved in 46 patients in Group 1 (57.5%) compared with 19 patients (23%) in group 2 (p=0.001). The average number of dressings used was 19 in stitch group compared with 30 in the non-stitch group (p=0.000). The average duration of healing in stitch group was 2.9 months compared with 5.7 months in non-stitch group (p=0.000). CONCLUSION: Stitching of neuropathic DFUs reduced the duration of wound healing and the frequency of wound dressing change.

Diabetic neuropathic forefoot and heel ulcers: management, clinical presentation and outcomes.

OBJECTIVE: The two most common sites for diabetic neuropathic foot ulcers are the forefoot and the heel. Each site has special characteristics that determines its course. The aim of this study is to compare clinical presentation, management and outcome of diabetic neuropathic forefoot ulcers to diabetic neuropathic heel ulcers. METHOD: This was a prospective cross-sectional comparative study carried in Jabir Abu Eliz Diabetic Centre (JADC), Khartoum, Sudan. A hundred patients with neuropathic diabetic ulcer were included, half were forefoot ulcers and the other half were hindfoot ulcers, two patients were lost on follow-up from each group. Neuropathy was graded using 10g monofilament nylon. Patients with vascular ischaemia, ankle brachial index pressure (ABPI) <0.9 and >1.1 were excluded. Other patient's data included demographic, foot and ulcer characteristics, comorbidities and outcomes. Foot ulcers were categorised according to Wagner classification, site and size of ulcer and presence of infection. Comorbidities evaluated included hypertension, ischaemic heart disease and renal impairment. All patients received standard wound care and regular follow-up. RESULTS: The age of the studied patients was 54.3 ± 11 years (mean ± standard deviation (SD 11)) and 52.9 ± 11 years for forefoot and heel ulcer respectively. The mean duration of diabetes was 12.4 ± 6 years for forefoot ulcers and 13.3 ± 7 years for heel ulcer. The mean duration of foot ulcer was 21 and 26 days for forefoot and heel respectively. Forefoot ulcers healed within 12 week in 45% of patients and by 20 weeks in 63%, while 35% of heel ulcers healed by 12 weeks and 54% healed by 20 weeks (p=0.058). Based on Wagner classification, healing was best in class 1 among both forefoot and heel ulcers, 22.4% and 12.2% respectively (p=0.003 for forefoot and 0.002 for heel). First and second metatarsal heads were the common site of forefoot ulcer. Heel ulcers >3cm dimension had longer duration of healing compared to forefoot ulcers at both 12 and 20 weeks (p<0.02). CONCLUSION: Healing in diabetic neuropathic forefoot ulcer was better than heel ulcer, though not reaching statistically significant value. Wagner class 1 had the best healing among both ulcers and a heel ulcer >3cm had a significantly longer healing time. DECLARATION OF INTEREST: The authors have no conflict of interest to declare.

Carbohydrate antigens as potential biomarkers for the malignancy in patients with idiopathic deep venous thrombosis: a retrospective cohort study.

A variety of biomarkers have been identified in recent prospective and retrospective reports as being potentially predictive of venous thromboembolis (VTE), particularly idiopathic deep venous thrombosis (IDVT). This study identified a serum tumor biomarker for early screening of IDVT. A total of 128 IDVT patients (54 females and 74 males; average age: 50.9±17.4 years) were included. Carcinoembryonic antigen (CEA), ferritin, ß2-microglobulin, cancer antigen (CA) 125, CA 15-3, CA 19-9, squamous cell carcinoma antigen (SCC), alpha-fetoprotein (AFP), prostate specific antigen (PSA), free PSA (f-PSA), and beta-human chorionic gonadotropin (ß-HCG) in patients with IDVT were detected. Malignancies were histo- or cytopathologically confirmed. Of the 128 IDVT patients, 16 (12.5%) were found to have malignancies. Serum CEA, CA 125, CA 15-3, and CA 19-9 were found to be helpful for detecting malignancies in IDVT patients. Our study revealed a positive association between these markers and tumors in IDVT patients. On the other hand, SCC and AFP were not sensitive enough to be markers for detecting tumors in patients with IDVT. No significant differences were found in positive rates of ferritin and ß2-microglobulin between tumor and non-tumor groups, and no significant difference exists in serum levels of ferritin and ß2-microglobulin between the two groups. Carbohydrate antigens, CA 15-3 in particular, may be useful for differential diagnosis and prediction of malignancies in patients with IDVT.

Enhanced adsorption of carbon sphere by doping with titania nanotubes for crystal violet removal: isotherm, kinetics, and thermodynamic studies.

In this study, the carbon sphere (Cs) has been prepared and modified by titania nanotubes (TNTs) to be utilized as an adsorbent toward crystal violet (CV) dye as a model for cationic dyes from aqueous solution. The prepared TNTs@Cs composites has been characterized by various techniques such as XRD, SEM, and TEM analysis. The adsorption analysis displayed that the adsorption capacity of CV dye onto the modified Cs with TNTs is 92.5 mg g-1, which is much higher than that achieved by pristine Cs (12.5 mg g-1). Various factors that influence the overall adsorption processes, such as pH, contact time, initial CV dye concentration, adsorbent weight, and temperature, were studied. The TNTs@Cs76.7 composite showed the highest removal percentage of 99.00% at optimum conditions. The adsorption isotherm analysis showed that the experimental data of adsorption CV dye fitted better with the Langmuir isotherm model with R 2 of 0.999, and the estimated maximum adsorption capacity was 84.7 mg g-1. On the other hand, the adsorption kinetic study showed that the adsorption of CV follows the pseudo-second order kinetic model with an equilibrium adsorption capacity (q e) of 10.66, 18.622, 47.61, and 48.31 mg g-1 for Cs, TNTs@Cs93, TNTs@Cs86.8, and TNTs@Cs76.7 composites, respectively. The thermodynamic analysis showed negative free energy (ΔG) values, this indicates that the adsorption of CV is a spontaneous and feasible process. Furthermore, the ΔH and ΔS are positive values that indicate an endothermic adsorption process. Furthermore, the prepared TNTs@Cs76.7 composite displayed remarkable adsorption stability and the removal efficiency of CV remains at 96.3% after five cycles.

Red blood cell alloimmunization in blood transfusion-dependent ß thalassemia major patients in Sana'a City-Yemen.

The development of erythrocyte alloantibodies complicates transfusion therapy in ß thalassemia major patients. These antibodies increase the need for blood and intensify transfusion complications. Data on erythrocyte alloimmunization is scarce in Yemeni thalassemia patients. We studied the frequency of alloimmunization in multitransfused ß-thalassemia major patients and investigated risk factors that affect antibody formation. Blood samples were taken from 100 ß thalassemia major patients who received multitransfused leukodepleted packed red-blood cells. Antibody screening and identification were performed by indirect antiglobulin test using the gel column technique. All patients were tested for autoantibodies using autocontrol and direct antiglobulin test. No adsorption test was done as no autoantibodies were detected in any patient. In our study of 100 ß-thalassemia patients, 50 were male and 50 were female with ages ranging from 1 to 30 years. Alloantibodies were present in 6% of patients, while no autoantibodies were detected. Of the 17 alloantibodies identified, the majority were directed against Kell (41.2%) and Rh (29.4%) blood groups. Alloimmunization was significantly associated with age group and sex (p = 0.013, p = 0.030), respectively in ß thalassemia major patients. The development of alloantibodies was not significantly associated with duration, total number of transfusions and splenectomy (P = 0.445, P = 0.125, P = 0.647). No autoantibodies found in patients with ß thalassemia major. The study found low rates of erythrocyte alloimmunization in multitransfused ß-thalassemia major patients, but significant alloantibodies were produced primarily from Kell and Rh blood groups, suggesting the need for providing phenotypically matched cells for selective antigens to improve transfusion efficiency.

The pharmacists' interventions after a Drug and Therapeutics Committee (DTC) establishment during the COVID-19 pandemic.

Introduction: Healthcare systems in developing countries faced significant challenges during COVID-19, grappling with limited resources and staffing shortages. Assessment of the impact of pharmaceutical care expertise, particularly in critical care units during the pandemics, in developing countries remains poorly explored. The principal aim of our study was to assess the impact of the Drug and Therapeutics Committee (DTC), comprising clinical pharmacists, on the incidence, types, and severity of medication errors and associated costs in using COVID-19 medications, especially antibiotics. Methods: An interventional pre-post study was carried out at a public isolation hospital in Egypt over 6 months. Results: Out of 499 medication orders, 238 (47.7%) had medication errors, averaging 2.38 errors per patient. The most frequent were prescribing errors (44.9%), specifically incorrect drug choice (57.9%), excessive dosage (29.9%), treatment duplication (4.5%), inadequate dosage (4.5%), and overlooked indications (3.6%). Linezolid and Remdesivir were the most common medications associated with prescribing errors. Pharmacists intervened 315 times, primarily discontinuing medications, reducing doses, introducing new medications, and increasing doses. These actions led to statistically significant cost reductions (p < 0.05) and better clinical outcomes; improved oxygen saturation, decreased fever, stabilised respiratory rates, and normalised white blood cell counts. So, clinical pharmacist interventions made a notable clinical and economic difference (66.34% reduction of the expenses) in antibiotics usage specifically and other medications used in COVID-19 management during the pandemic. Conclusion: Crucially, educational initiatives targeting clinical pharmacists can foster judicious prescribing habits.

The long coiled-coil protein NECC2 regulates oxLDL-induced endothelial oxidative damage and exacerbates atherosclerosis development in apolipoprotein E -/- mice.

Oxidized low density lipoprotein (oxLDL)-induced endothelial oxidative damage promotes the development of atherosclerosis. Caveolae play an essential role in maintaining the survival and function of vascular endothelial cell (VEC). It is reported that the long coiled-coil protein NECC2 is localized in caveolae and is associated with neural cell differentiation and adipocyte formation, but its role in VECs needs to be clarified. Our results showed NECC2 expression increased in the endothelium of plaque-loaded aortas and oxLDL-treated HUVECs. Down-regulation of NECC2 by NECC2 siRNA or compound YF-307 significantly inhibited oxLDL-induced VEC apoptosis and the adhesion factors expression. Remarkably, inhibition of NECC2 expression in the endothelium of apoE-/- mice by adeno-associated virus (AAV)-carrying NECC2 shRNA or compound YF-307 alleviated endothelium injury and restricted atherosclerosis development. The immunoprecipitation results confirmed that NECC2 interacted with Tyk2 and caveolin-1(Cav-1) in VECs, and NECC2 further promoted the phosphorylation of Cav-1 at Tyr14 b y activating Tyk2 phosphorylation. On the other hand, inhibiting NECC2 levels suppressed oxLDL-induced phosphorylation of Cav-1, uptake of oxLDL by VECs, accumulation of intracellular reactive oxygen species and activation of NF-κB. Our findings suggest that NECC2 may contribute to oxLDL-induced VEC injury and atherosclerosis via modulating Cav-1 phosphorylation through Tyk2. This work provides a new concept and drug target for treating atherosclerosis.

Dexamethasone-tamoxifen combination exerts synergistic therapeutic effects in tamoxifen-resistance breast cancer cells.

Tamoxifen (TAM) is a key player in estrogen receptor-positive (ER+) breast cancer (BC); however, ∼30% of patients experience relapse and a lower survival rate due to TAM resistance. TAM resistance was related to the over expression of SOX-2 gene, which is regulated by the E2F3 transcription factor in the Wnt signaling pathway. It was suggested that SOX-2 overexpression was suppressed by dexamethasone (DEX), a glucocorticoid commonly prescribed to BC patients. The aim of the present study is to explore the effect of combining DEX and TAM on the inhibition of TAM-resistant LCC-2 cells (TAMR-1) through modulating the E2F3/SOX-2-mediated Wnt signaling pathway. The effect of the combination therapy on MCF-7 and TAMR-1 cell viability was assessed. Drug interactions were analyzed using CompuSyn and SynergyFinder softwares. Cell cycle distribution, apoptotic protein expression, gene expression levels of SOX-2 and E2F3, and cell migration were also assessed. Combining DEX with TAM led to synergistic inhibition of TAMR-1 cell proliferation and migration, induced apoptosis, reduced SOX-2 and E2F3 expression and was also associated with S and G2-M phase arrest. Therefore, combining DEX with TAM may present an effective therapeutic option to overcome TAM resistance, by targeting the E2F3/SOX-2/Wnt signaling pathway, in addition to its anti-inflammatory effect.

Knowledge and Attitudes Regarding Crimean-Congo Hemorrhagic Fever Among Slaughterhouse Workers in Sana'a and Dhamar Cities-Yemen: A Cross-Sectional Study.

Background: Crimean-Congo Hemorrhagic Fever (CCHF) is a viral infection spread through tick bites or contact with secretions from infected animals or humans, posing a risk to slaughterhouse workers. This study aimed to evaluate the knowledge and attitudes of slaughterhouse workers in Yemen towards CCHF. Methods: A cross-sectional study conducted on 173 adults working at slaughterhouses in Sana'a and Dhamar cities, Yemen using a multi-stage sampling. The questionnaire used in the study was a reliable survey instrument (with a Cronbach's alpha coefficient of 0.71) employed for the purpose of data collection. The questionnaire encompassed three distinct sections: 1)- demographic inquiries pertaining to age, gender, marital status, level of education, and occupation; 2)- knowledge-based inquiries consisting of 27 items;3)- the attitude section consisted of 11 questions. After completing the questionnaire, the data were analyzed by SPSS version 24, using percentages, chi-square test, and Spearman correlation coefficient. Results: The mean age of the participants was 30.6 years with a SD of 11.2 years, with 84.4% male and 15.6% female. Most slaughterhouse workers were butchers (78.6%) and some were shepherds (21.4%). The participants had poor knowledge (86.7%) and attitude (72.3%) towards CCHF. There exists a noteworthy association between the knowledge scores and the gender, education level, and occupation (P=0.035, P=0.039, P=0.001). A significant positive correlation was identified between knowledge and attitude scores (r = 0.715, P<0.001). Conclusion: The majority of respondents had poor knowledge of CCHF. Educational programs are essential for increasing community awareness, with involvement of technical experts crucial for disseminating information on preventing and managing CCHF.