Osteomyelitis (OM) is a serious bacterial bone infection and can be life-threatening if not treated promptly. A promising approach to manage OM involves using drug-loaded fibrous implants or scaffolds containing antibiotics, analgesics, or anti-osteoporosis medications to combat infection, reduce pain and promote bone healing, respectively. In this study, a coaxial electrospinning technology was employed to fabricate drug-loaded fibers encapsulating vancomycin hydrochloride (VAN), an antibiotic, and diclofenac sodium (DIC), an analgesic to prevent infection and alleviate post-surgical pain. The fibers were characterized using scanning electron microscopy (SEM) which indicated that the drug-loaded (DL) coaxial fibers had smooth surfaces and lacked beads and pores. The drug loading of the DL coaxial fibers was estimated by high-performance liquid chromatography (HPLC), and the results were calculated as 75 ± 4 µg/mL for VAN and 82 ± 3 µg/mL for DIC. The drug release was also measured by HPLC, which showed a rapid initial release, i.e., 59% for VAN and 75% for DIC within the first day, followed by a sustained slow release reaching approximately 92% and 79%, respectively after 264 h. The antimicrobial assay zone of inhibition confirmed the antibacterial activity of the DL fibers against Staphylococcus aureus. The cell viability assessments on the drugs alone against human dermal fibroblasts (HFF-1) demonstrated that the VAN and DIC combination is safe at concentrations up to 250 µg/mL but required careful dosing due to time-dependent cytotoxicity. Overall, the study highlights the potential use of VAN and DIC-loaded coaxial electrospun fibers as a localized drug delivery system for OM treatment, offering controlled drug release, effective antibacterial action, and biocompatibility.

Practically, all patients treated with Minoxidil (MXD) reported experiencing hypertrichosis, even though the original intended usage of the drug was the treatment of hypertension. This limitation supports the potential of repurposing MXD as a topical agent for the treatment of hair loss. Accordingly, the outset of the current study was to exploit the cutaneous influence of MXD and limit the drawbacks of conventional available dosage forms. This could be achieved via developing a nanocarrier, mainly; nanoemulsion (NE) for transdermal delivery of MXD. Therefore, several NEs were prepared containing MXD and optimized according to their particle size and in vitro release study using Response Surface Methodology. The optimized formulation was examined for its organoleptic properties, pH, viscosity, and drug content. Moreover, Morphology, kinetic study was investigated a long with the stability testing upon keeping in two distinct settings: room temperature and refrigerator for 12 months. Eventually, the in vivo hair growth rate was monitored and documented for 28 days in pretreated mice. The developed MXD-NEs were developed and optimized using Box Behnken Design software to obtain the most desired formula. The optimized MXD-NE demonstrated a nanosize (83.1 nm) and performs a successful in vitro release (75.6%) over a period of 6 h. Additionally, it showed ideal physical properties with pH (5.9), viscosity (26.7 cP), and drug content (99.4%). The droplets in the formula seemed to be spherical. The formula was stable when preserved for 12 months at both applied conditions. Finally, the formula demonstrated significant faster rate of hair growth that mostly owed to the value of nanocarrier in delivering drug into follicular hairs.

While several anti-tumor biosimilars have been approved in China, comprehensive nationwide analyses of their real-world utilization patterns remain limited, particularly regarding cross-regional adoption and indication-specific usage. We collected information on patients treated with bevacizumab, rituximab, trastuzumab and their biosimilars at 109 hospitals in nine Chinese cities from 2019 to 2023. Analysis of 264,527 prescriptions revealed rapid biosimilar adoption for bevacizumab (2023 originator share: 20.0%, -25.1%/year), moderate for rituximab (32.1%, -16.8%/year), and limited for trastuzumab (70.0%, -8.3%/year). Geographic variation was substantial (2023 city ranges: bevacizumab 2.3-43.0%; rituximab 6.7-70.3%; trastuzumab 42.4-92.4%). Tertiary hospitals showed faster biosimilar uptake than secondary hospitals (bevacizumab: + 23.7%). Free medical care patients preferred originators (bevacizumab: 64.1% vs 38-39% for other payers). Off-label use demonstrated significantly higher biosimilar adoption (bevacizumab: 69.0%; rituximab: 52.1%) versus approved indications (p < 0.00625). Cost distributions mirrored prescription trends but consistently favored originators. All trends were statistically significant (p < 0.05). The biosimilar market share showed steady annual growth, however the growth rates vary across different products. However, Patients with lower out-of-pocket costs remained more likely to choose original products. Enhanced regulatory oversight of both approved and off-label/extrapolated indications is needed to ensure appropriate biosimilar utilization.

There is a need for assessing the impact of current drug availability regulations across the various stages of the pharmaceutical supply chain and among different stakeholders involved. This mixed methods survey assessed the impact of pharmaceutical availability regulations across the drug supply chain in Saudi Arabia. This research utilized a cross-sectional study design involving a survey conducted at a single point in time to collect data from key stakeholders across the various stages of the pharmaceutical supply chain. Various metrics, such as availability ratings, accessibility issues, and stakeholder perspectives on regulatory effectiveness were examined. Mixed methods analysis combined survey statistics with qualitative insights. The data source for this study comprised an online survey targeting key stakeholders involved along the pharmaceutical supply chain (n = 27), including drug manufacturers (n = 10), distributors (n = 4), and healthcare settings, such as hospitals (n = 9) and pharmacies (n = 4). The data were collected in September 2023. Manufacturers (mean availability rating of 3.8) and distributors (mean availability rating of 3.5) viewed regulations to be more effective versus hospital/pharmacies (mean availability rating of 3.3) citing lack of harmonization and transparency as key efficiency deterrents. Centralized inventory monitoring and unified availability benchmarks were strongly advocated as enhancements alongside improved communication flows. Ultimately, a collaborative, yet guided approach is imperative for balancing industrial priorities and access imperatives to attain synchrony across the pharmaceutical value chain in order to augment both health and economic outcomes.

Artemisia sieberi Besser (A. sieberi) has shown promise as a natural source of safe cytotoxic agents for breast cancer therapy. However, its effects on triple-negative breast cancer (TNBC), a very aggressive subtype lacking targeted treatments, remain poorly studied. This study evaluates the anticancer activity of A. sieberi extracts against the MDA-MB-231 TNBC cell line, comparing results with hormone receptor-positive MCF-7 cells. Aerial parts of A. sieberi were extracted using ethanol and methanol and then chemically characterized via gas chromatography/mass spectrometry (GC/MS) to identify bioactive compounds. Cytotoxic effects were assessed using cell viability assays, while apoptosis induction was examined through flow cytometry (Annexin V/propidium iodide staining), caspase-3/-7 activation assays, and mitochondrial membrane permeabilization visualized using confocal microscopy. Western blotting analyzed the expression levels of apoptotic proteins. In silico molecular docking simulations explored the interactions between phytochemicals and apoptosis-regulating proteins. A. sieberi extracts exhibited higher cytotoxicity against MDA-MB-231 cells than against MCF-7 cells, with lower IC values. Treatment of TNBC cells induced apoptosis, evidenced by increased caspase activity, mitochondrial membrane permeabilization, elevated Bax, and decreased Bcl-2 expression. Additionally, colony formation assays demonstrated a significant reduction in tumorigenic potential. Computational analyses indicate that β-sitosterol and stigmasterol, among the main compounds, exhibited strong interactions with apoptosis regulators by docking with Bcl-2, supporting their promising anticancer potential. A. sieberi extracts induce potent apoptosis and exert anti-tumour effects in TNBC cells, highlighting their potential as sources of novel anticancer agents. Further isolation and characterization of active constituents are warranted for therapeutic development.

Colistin is an antibiotic that belongs to the polymyxin family. It has reemerged as a treatment of last resort against multi-drug resistant gram-negative bacterial infections. Nephrotoxicity remains the most daunting and limiting adverse effect of colistin therapy leading to treatment discontinuation and mortality in high-risk patients. Nephrotoxicity occurs secondary to the accumulation of colistin in the renal proximal tubular epithelial cells (RPTECs). Mechanistically, colistin exerts endoplasmic reticulum and ribotoxic stress, induces mitochondrial dysfunction and oxidative stress in the RPTECs leading to apoptosis and necrosis. Moreover, colistin activates the mitogen-activated protein kinases and perturbs the balance between survival-promoting and death-promoting growth factors. In this review we have presented and integrated the major in vitro and in vivo mechanistic studies undertaken to study colistin-induced nephrotoxicity. In addition, we have suggested a possible unifying mechanism for colistin renal toxicity based on the emerging concept of the cross-organelle stress response.

Erlotinib (ERL) and Gefitinib (GEF) are weakly basic drugs with pH-dependent solubility profiles mainly dependent on stomach pH. We proposed possible drug and/or food-drug interactions with acidifying agents. Citric acid (CA) and phosphoric acid (PPA) are the most common acidifying agents used in food and medication to treat certain conditions. This study evaluated the impact of concomitant consumption of CA and PA on ERL and GEF pharmacokinetic parameters (PKs). The PKs of ERL and GEF were investigated in rats after four weeks of CA and PPA consumption in low (175 mg/kg) and high (100 mg/kg) doses using UPLC-MS/MS. Data indicated that acidifying agents altered PKs of ERL and GEF dose-dependently. High doses of CA and PPA significantly increased the Cmax of ERL by 103% and 218%, the AUC by 35% and 78%, respectively, while reducing CL/F by 44% with CA and 74% with PPA. For GEF, Low and high doses of PPA increased C and T with a reduction of CL/F. A low dose of CA did not impact C, significantly decreased AUC (28%), and increased CL/F (16%). The high dose of CA increased C (13%) with no impact on AUC and decreased CL/F (23%). Furthermore, both doses of acidifying agents significantly increased liver enzyme levels and reduced body weight within two weeks. The results demonstrated that the PKs of both drugs were changed, and caution and close monitoring should be taken with ERL and GEF when co-administered with an acidifying agent.

A novel class of antidiabetic drugs known as sodium-glucose cotransporter 2 inhibitors (SGLT2-Is) prevents the renal proximal tubules from reabsorbing glucose. While a recent study showed that SGLT2-Is may be able to slow the proliferation of cancer cells that express SGLT2, limited evidence exists regarding their effects on renal cell carcinoma (RCC). Here, we examine the ability of the SGLT2-I canagliflozin (Cana) to prevent experimentally induced kidney carcinogenesis in male rats. A total of twenty-four rats were divided into four groups, six in each: negative control, DEN/TAA control; rats (60-70 g) were fed a choline-deficient diet (CDD) for 4 weeks, then rats were subjected to four doses of 50 mg/kg diethyl nitrosamine (DEN) over 8 weeks followed by thioacetamide 100 mg/kg (TAA) intraperitoneal injections twice weekly for 15 weeks, treated groups: rats were given canagliflozin (10 and 20 mg/kg b.wt.) orally starting from the 24th week of the experiment till the end of the 29th week. The obtained findings showed that treatment with canagliflozin reduced renal oxidative stress and toxicity indicator levels and considerably reinforced renal antioxidant capacity. The histological changes further supported the biochemical findings. In addition, canagliflozin therapy activated AMPK and inhibited Nrf2, NLRP3 and IL-6/STAT3 pro-inflammatory pathway. Immunohistochemistry exhibited upregulation of pro-apoptotic protein caspase-3 and downregulation of PCNA expression in Cana-treated groups. Conclusion: the results showed that canagliflozin has anti-carcinogenic efficacy against renal carcinogenesis via activating AMPK and suppressing NLRP3/IL-6/STAT3 signaling pathways.

This study aimed to establish a method for quantifying baicalin (BC) in rabbit ocular tissues and plasma, and evaluate the pharmacological efficacy and pharmacokinetic properties of BC and BC@HS15/DSPE-PEG2000-L-Val, a novel ocular formulation for dry eye treatment. BC@HS15/DSPE-PEG2000-L-Val or free BC was administered via eye drops to benzalkonium chloride (BAC)-induced dry eye mice. Corneal and conjunctival tissues were assessed for anti-dry eye efficacy. BC concentrations in cornea, conjunctiva, aqueous humor, and ocular plasma were quantified using LC-MS/MS. Noncompartmental pharmacokinetic parameters (AUC, Tmax) were calculated using DAS 2.0 software. The method demonstrated excellent linearity (0.50-500.00 ng/mL, r > 0.9905), precision (RSD < 10%), and accuracy (± 13%). Compared to free BC, BC@HS15/DSPE-PEG2000-L-Val significantly increased tear secretion, reduced MMP-3/MMP-9 expression, and preserved corneal epithelium integrity. In the micelle group, corneal and conjunctival Cmax values were 2.7- and 3.6-fold higher than the solution group, respectively. A sensitive and validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to measure baicalin concentrations in ocular plasma and tissues of rabbits. BC@HS15/DSPE-PEG2000-L-Val for treating dry eye demonstrated significantly superior outcomes. The nano-micelle notably enhanced BC concentration on the ocular surface and effectively prolonged its retention time.

Antimicrobial resistance (AMR) is rising alarmingly in Saudi Arabia, as evidenced by surveillance data. This retrospective cohort study evaluated the association between parenteral antimicrobial use and bacterial resistance at King Khaled Hospital, Al-Kharj, using electronic health records. Linear regression analyzed antibiotic exposure-resistance relationships over 36 months (January 2022-December 2024). Eligible participants were hospitalized ≥ 48 h and received ≥ 1 parenteral antimicrobial. The required sample size was 384 (calculated via Cochran's formula). Inclusion mandated laboratory-confirmed bacterial infections (positive cultures with susceptibility testing). Investigated pathogens included Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, and Staphylococcus aureus. Among 4,007 participants, 59.02% were female, and 73.07% were Saudis. Findings revealed severe AMR, particularly in Escherichia coli and Klebsiella pneumoniae, with high resistance to multiple antibiotic classes. Acinetobacter baumannii exhibited near-pan-drug resistance (> 90% resistance to most antibiotics). Imipenem use strongly correlated with Escherichia coli resistance (R = 1.000, p-value = 0.009), indicating significant carbapenem-driven selection pressure. Meropenem exposure also closely linked to Klebsiella pneumoniae resistance (R = 0.994, p-value = 0.050). Widespread resistance to β-lactams, fluoroquinolones, and aminoglycosides-combined with near-pan-resistant Acinetobacter baumannii-highlights escalating treatment challenges. Crucially, carbapenem usage (imipenem/meropenem) strongly predicted resistance in Escherichia coli and Klebsiella pneumoniae, reinforcing antimicrobial pressure's role in resistance development. These results emphasize the urgent need for antimicrobial stewardship at King Khaled Hospital to curb carbapenem overuse and combat resistant infections.

Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are a novel group of oral medications used to treat type 2 diabetes mellitus (T2DM). Nonalcoholic fatty liver disease (NAFLD), a complication of T2DM, is now recognized as one of the most frequent causes of chronic liver disorders. We aimed to investigate the effects of SGLT2is on hepatic function and glucose homeostasis in patients with T2DM and comorbid NAFLD. To our knowledge, this is the first study in the Arab region to compare the effects of SGLT2is and other antidiabetic medications and to evaluate the outcomes after a 6-month follow-up period in this patient cohort. This cohort study involved 100 patients with T2DM. The patients were divided equally into two groups. The exposed group comprised 50 patients receiving any of the SGLT2is (empagliflozin or dapagliflozin); the non-exposed group comprised 50 patients taking any other oral antidiabetic medication (other than glucagon-like peptide-1 receptor agonists or SGLT2is). The outcomes investigated were glycemic control, hepatic function, and liver fibrosis parameters, investigated at baseline and after 6 months. Significant improvements in glycemic control, hepatic function, and fibrosis parameters were observed in the SGLT2i group after 6 months, as evidenced by laboratory and clinical data (p < 0.001). Significant improvements were observed in hemoglobin A1c, Fibrosis-4 index, gamma-glutamyl transferase level, alanine aminotransferase level, and NAFLD fibrosis score (p < 0.05). The findings indicate that 6 months of SGLT2i therapy improved fibrosis and glucose homeostasis in patients with T2DM and NAFLD. Therefore, SGLT2is are effective therapeutic agents in this patient population.

In Saudi Arabia, the regulation of community pharmacies currently falls under the Ministry of Health (MOH). There is a need to shift the regulatory framework of community pharmacies to be under the Saudi Food and Drug Authority (SFDA) to align with global standards. However, there is limited knowledge about the perceptions of pharmacists regarding the current regulatory framework in community pharmacies in the Kingdom of Saudi Arabia (KSA).

Durvalumab is an immune checkpoint inhibitor that targets PD-L1 and is used for malignancies such as hepatocellular carcinoma. Although effective, it may cause immune-related adverse events, including rare cases of myocarditis (0.06% to 1%), which usually appear early. This complication results from immune response-induced damage to the myocardium, highlighting the importance of prompt detection and management to prevent potentially fatal outcomes. This report describes a 70-year-old woman with advanced hepatocellular carcinoma who developed myocarditis after receiving a single dose of durvalumab. The patient presented with atypical chest pain, shortness of breath, and gastrointestinal symptoms. Initial investigations revealed elevated cardiac biomarkers, including Troponin I and CK-MB, and an ECG showing sinus tachycardia and right bundle branch block. A cardiac MRI confirmed non-ischemic myocardial injury, leading to a diagnosis of ICI-induced myocarditis. The patient was treated with high-dose corticosteroids, resulting in rapid clinical improvement and stabilization of cardiac function. A multidisciplinary approach involving cardiology, oncology, and clinical pharmacy was crucial in managing this complex case. This case highlights the importance of heightened vigilance among healthcare providers when administering ICIs, particularly durvalumab, due to the risk of myocarditis. Early detection and prompt intervention are essential to manage ICI-related adverse events and prevent severe outcomes. The successful treatment of this patient demonstrates the importance of a multidisciplinary approach in tackling the complexities of ICI-induced myocarditis. Further research is necessary to optimize management strategies and follow-up protocols for patients experiencing this rare but serious adverse event.

The accumulation of pathological markers, such as tau tangles and amyloid-beta (Aβ) plaques, and progressive cognitive dysfunction are the markers of Alzheimer's disease (AD). The development of successful therapeutic plans requires exposure to the molecular mechanisms underlying AD development. The importance of non-coding RNAs (ncRNAs), such as circular RNAs (circRNAs), microRNAs (miRNAs), long ncRNAs (lncRNAs), and PIWI-interacting RNAs (piRNAs), in controlling gene expression and influencing the pathophysiology of disease has been brought to light by recent studies. With a focus on their role in important processes such tau hyperphosphorylation, neuroinflammation, and amyloid-beta formation, this study attempts to give a thorough overview of the several types of ncRNAs and their dysregulation in AD. The genetic variants that are associated with the function of ncRNA including single nucleotide polymorphisms (SNPs) may influence ncRNA expression and activity, thereby impacting the susceptibility of individual towards AD. Furthermore, the impact of biomarkers of ncRNAs for early diagnosis and therapeutic option for intervention, highlighting most recent advancement in high-throughput technologies and bioinformatics facilitating ncRNA profiling has also being discussed. The integration of multi-omics approaches and artificial intelligence, new advancement for the complex relationship among ncRNAs and AD pathology are also discussed. The enhancement and understanding of ncRNAs could lead to the door for novel therapeutic concepts for the mitigation of AD progression, offering effective interventions in a disease that currently starves the curative treatments.

Pharmacists are recognized as specialists in medications and are responsible for maintaining drug safety. A recent study showed that Egyptian community pharmacists face several barriers to the spontaneous reporting of adverse drug reactions (ADRs). This study aimed to identify the potential facilitators perceived by community pharmacists in Egypt that could enhance ADR reporting and contribute to the development of national ADR data. A cross-sectional survey was conducted using a self-administered questionnaire distributed to 1,316 community pharmacists in Egypt. Of the 905 respondents (68.7% response rate), only 125 (13.8%) revealed they had reported an ADR, with 30 (24.4%) being unable to correctly identify ADR types and 34 (27.2%) reporting they lacked the training required to do so. Key facilitators identified be respondents included ensuring that ADR-related training is available from universities (95.7%), the Egyptian Pharmacists Syndicate (91.9%), and peer-reviewed journal articles (90.6%). Participants advocated for simplifying the reporting process (92.5%), providing clear instructions (92.8%), having access to a smartphone application (80.0%), receiving regular reminders (92.4%) having their role promoted in the media (95.6%). Community pharmacists are crucial in ADR reporting, especially in low-to-middle-income countries e.g. Egypt. The study identified several facilitators to improve reporting practices, including educational interventions, process enhancements, and motivational strategies. Implementing these facilitators could address underreporting and data inaccuracies.

GLP-1 receptor agonists represent a breakthrough for managing type-2 diabetes and obesity, offering metabolic benefits across multiple organ systems. These medications provide effective glycaemic control, significant weight reduction, and cardiovascular protection through complex signalling pathways affecting pancreatic, gastrointestinal, neural, and cardiovascular tissues. Their therapeutic potential extends beyond metabolic disorders. Clinical studies demonstrate substantial decreases in HbA1c, body weight (15-20%), and cardiovascular events compared to traditional treatments. Emerging applications include non-alcoholic fatty liver disease and neurodegenerative conditions. Significant barriers still exist despite established safety profiles, such as high costs that restrict access worldwide, a lack of predictive biomarkers for treatment response, a lack of knowledge about the mechanistics of gut microbiota interactions, and an incomplete understanding of long-term safety, particularly with regard to thyroid and pancreatic effects. Research gaps include appropriate patient classification, cost-effectiveness across healthcare systems, and established methodologies for developing applications. Potential future developments include novel delivery mechanisms, multi-receptor agonists, and a broader range of therapeutic uses for the treatment of metabolic disorders and their consequences. From their identification as incretin hormones to development of long-acting analogue, GLP-1 agonists have revolutionized metabolic disease management. Their pleiotropic benefits arise from intricate signalling cascades that regulate appetite, insulin secretion, and energy homeostasis across multiple tissues.

Malaria remains a significant public health challenge in regions where it is endemic. Pregnant women and young children are particularly vulnerable to the disease. Effective and timely diagnostic methods are crucial for reducing severe health outcomes. These methods help prevent deaths and lessen the widespread clinical and epidemiological burden on at-risk populations. However, traditional methods involved in the process of malaria parasite detections such as microscopic examination of blood smear by medical trained technicians is known to be time consuming, purely subjective and highly prone to errors. Therefore, Artificial Intelligence (AI) based OD (Object Detection) model like YOLO are preferred for overcoming these issues faced by traditional approaches as YOLO is known to be more rapid and precise by predicting bounding boxes and class probabilities than other models. However, existing YOLO model face challenges such as higher localization error, struggle with small objects and better accuracy of the model. Therefore, proposed research work focuses on employing YOLOv3 model with modified MobileNetv2 in backbone structure for classifying Plasmodium vivax (P. vivax) cells with the aim of improving the performance and speed of the model for detecting objects as MobileNetv2 is known for its faster processing and reduced resource consumption. However, accuracy is still measured as one of the key downsides for detecting and classifying the classes of thin blood smear, therefore modified MobileNetv2 is used, where proposed TCL (Transformed Convolution Layer) is employed at bottleneck layer, where weights are calculated based on different classes of image features thereby making the process more effective for classifying the infected and uninfected malaria cells of thin blood smear images effective. Besides, the performance of the proposed model is evaluated by implementing different metrics where the findings obtained are accuracy value of 1.00, precision value of 0.98, recall of 0.98, F1 score of 0.97 and mean average precision (mAP) value of 0.90. The major contribution of the study focuses on providing a better diagnostic approach for medical professionals in order to obtain improved results.

Neurodermatitis and chronic eczema are characterized by severe itching and can lead to complications such as skin infections and folliculitis. Current treatment primarily involves glucocorticoid analogs which may be associated with side effects and lack of effective delivery strategies. The suspended ointment developed in this study aims to address these issues, offering improved therapeutic outcomes. The present study aimed to investigate the relationship between formulation/process variables versus the content uniformity and viscosity of neomycin sulfate and triamcinolone acetonide ointments and to explore the feasibility of using an in vitro approach to assess product sameness. Monofactor analysis was used to evaluate the impact of formulation and process variables. The new formulation was evaluated in terms of the prescription process, quality, stability, in vitro drug release behavior, and distribution of skin. The optimal prescription composition was 0.54% neomycin sulfate, 0.10% triamcinolone acetonide, 5.08% substrate A and 94.28% liquid paraffin. Quality and stability assessments confirmed that the formulation met the required standards for appearance and composition. Mathematical modeling of the drug release profile indicated that the release kinetics evaluated using the vertical diffusion cell method, closely aligned with first-order kinetics. Raman spectroscopy confirmed the successful penetration of triamcinolone acetonide into the skin, triamcinolone acetonide works primarily in the skin. Furthermore, skin irritation tests demonstrated that the formulation caused no detectable irritation. These results demonstrate that it can be a promising drug in treating neurodermatitis and chronic eczema.

Methicillin-resistant Staphylococcus aureus (MRSA) is a major pathogen associated with antimicrobial resistance, particularly in bloodstream infections affecting individuals with underlying conditions such as sickle cell disease (SCD). Resistance to tetracycline and erythromycin in MRSA is often mediated by efflux pump genes, including tetK, tetM, ermA, and ermC. These genes play a crucial role in reducing the efficacy of commonly used antibiotics, posing significant challenges in clinical management. Understanding the genetic variations within these resistance genes and their association with phenotypic resistance patterns is essential for guiding effective treatment strategies and improving patient outcomes. However, earlier research has not thoroughly examined how changes in the genes tetK, tetM, ermA, and ermC relate to the antibiotic resistance seen in MRSA strains taken from SCD patients. This gap indicates that there must be a focused investigation to bridge the current knowledge deficit and support the development of more targeted therapeutic approaches. This study aimed to investigate the prevalence and genetic basis of antibiotic resistance in MRSA bloodstream isolates from sickle cell disease patients in Riyadh, Saudi Arabia. It looked at the resistance genes, like tetK, ermA, and ermC, and studied how changes in their sequences affected them using evolutionary and structural analysis over seven years. MRSA isolates (n = 34) were obtained from 3,979 SCD patients (2017-2024). Representative strains were analyzed for their antibiotic susceptibility using the VITEK 2 system and PCR-based identification of resistance genes (e.g., tetK, tetM, ermA, and ermC). Among SCD patients, 0.9% exhibited MRSA bloodstream infections, predominantly affecting individuals over 20 years of age. During our study, we made an intriguing discovery that the toxin genes (hlg, hla, Pvl, and sea) were predominant in the MRSA isolates. Sequencing of tetK, ermA, ermC, and 16S rRNA genes was performed, and variations were analyzed using bioinformatics tools (BLAST, MEGA X, CARD, BLASTX). Phylogenetic analysis was conducted, and the results were correlated with phenotypic resistance profiles. All isolates were resistant to β-lactam antibiotics but sensitive to vancomycin and tobramycin. The analysis of the genetic sequence revealed important changes in the tetK gene, with strain RHD-KSA30 exhibiting several different amino acids. Phylogenetic analysis grouped Riyadh strains into distinct clusters. Variations in tetK correlated with differential susceptibility to antibiotics like erythromycin, clindamycin, and ciprofloxacin. The genetic diversity of the tetK gene in MRSA strains and its function in mediating antibiotic resistance are highlighted in this study. Although vancomycin and tobramycin are still effective treatments, the resistance to other antibiotics shows the need for continuous monitoring and the development of tailored treatment plans, especially for high-risk groups like patients with sickle cell disease (SCD).

Limited research has explored the genetic variability of CYP3A4 and CYP3A5 in the Saudi population, particularly concerning tacrolimus (Tac) therapy among Saudi kidney transplant patients (SKTP).

Triple-negative breast cancer (TNBC) presents ongoing clinical challenges, often leading to relapse in many patients. The relapse is partly explained by tumor cells transitioning into a senescent state following chemotherapy or radiation, resulting in a more aggressive phenotype, contributing to disease recurrence. Consequently, combining senolytics with traditional treatments could be a viable and promising strategy in treating TNBC. To address this, we induced therapy-induced senescence (TIS) both in vitro and in vivo by combining the poly ADP-ribose polymerase (PARP) inhibitor talazoparib with radiation. We tested whether exposure to the senolytic agent, venetoclax, would result in the eradication of senescent cells and augmentation of apoptosis. TIS Markers, like senescence-associated beta-galactosidase (SA-β-gal), CDKN1A, and senescence-associated secretory phenotype (SASP) marker IL-6, were altered following talazoparib and radiation in both 4T1 and MDA-MB-231 TNBC cell lines. Interestingly, venetoclax treatment following TIS induction led to pronounced apoptotic cell death and significant changes in SA-β-gal and IL-6, implying enhanced sensitivity post-senescence induction. Furthermore, these data were validated in vivo in an immunocompetent TNBC-bearing mouse model, in which venetoclax alone had a modest effect on growth inhibition. However, when combined with radiotherapy/talazoparib, venetoclax dramatically interfered with tumor recovery post-senescence induction, indicating a potential strategy to mitigate disease recurrence. These results suggest that combining radiotherapy with PARP inhibitors with senolytic agents such as venetoclax could potentially overcome disease relapse associated with TNBC.