High-Performance Bioinspired Microspheres for Boosting Dental Adhesion.

Dental adhesives are widely used in daily practice for minimally invasive restorative dentistry but suffer from bond degradation and biofilm attack. Bio-inspired by marine mussels having excellent surface-adhesion capability and high chemical affinity of polydopamine (PDA) to metal ions, herein, experimental zinc (Zn)-containing polydopamine-based adhesive formulation, further being referred to as "Zn-PDA@SiO2 "-incorporated adhesive is proposed as a novel dental adhesive. Different Zn contents (5 and 10 mm) of Zn-PDA@SiO2 are prepared. Considering the synergistic effect of Zn and PDA, Zn-PDA@SiO2 not only presents excellent antibacterial potential and notably inhibits enzymatic activity (soluble and matrix-bound proteases), but also exhibits superior biocompatibility and biosafety in vitro/vivo. The long-term bond stability is substantially improved by adding 5 wt% 5 mm Zn-PDA@SiO2 to the primer. The aged bond strength of the experimentally formulated dental adhesives applied in self-etch (SE) bonding mode is 1.9 times higher than that of the SE gold-standard adhesive. Molecular dynamics calculations indicate the stable formation of covalent bonds, Zn-assisted coordinative bonds, and hydrogen bonds between PDA and collagen. Overall, this bioinspired dental adhesive provides an avenue technology for innovative biomedical applications and has already revealed promising perspectives for dental restorative dentistry.

Genetic diversity of macrolides resistant Staphylococcus aureus clinical isolates and the potential synergistic effect of vitamins, C and K3.

BACKGROUND: Macrolide antibiotics have been extensively used for the treatment of Staphylococcus aureus infections. However, the emergence of macrolide-resistant strains of S. aureus has become a major concern for public health. The molecular mechanisms underlying macrolide resistance in S. aureus are complex and diverse, involving both target site modification and efflux pump systems. In this study, we aim to overcome the molecular diversity of macrolide resistance mechanisms in S. aureus by identifying common molecular targets that could be exploited for the development of novel therapeutics. METHODS: About 300 Staphylococcus aureus different isolates were recovered and purified from 921 clinical specimen including urine (88), blood (156), sputum (264), nasal swabs (168), pus (181) and bone (39) collected from different departments in Tanta University Hospital. Macrolide resistant isolates were detected and tested for Multi Drug Resistant (MDR). Gel electrophoresis was performed after the D test and PCR reaction for erm(A), (B), (C), msr(A), and mph(C) genes. Finally, we tried different combinations of Erythromycin or Azithromycin antibiotics with either vitamin K3 or vitamin C. RESULTS: Macrolide resistance S. aureus isolates exhibited 7 major resistance patterns according to number of resistance markers and each pattern included sub patterns or subgroups. The PCR amplified products of different erm genes; analysis recorded different phenotypes of the Staphylococcus aureus isolates according to their different genotypes. In addition, our new tested combinations of Erythromycin and vitamin C, Erythromycin, and vitamin K3, Azithromycin and vitamin C and Azithromycin and vitamin K3 showed significant antibacterial effect when using every antibiotic alone. Our findings provide new insights into the molecular mechanisms of macrolide resistance in S. aureus and offer potential strategies for the development of novel protocols to overcome this emerging public health threat.

Clinical and endoscopic characteristics of patients undergoing gastrointestinal endoscopic procedures in Egypt: a nationwide multicenter study.

BACKGROUND: Egypt faces a significant public health burden due to chronic liver diseases (CLD) and peptic ulcer disease. CLD, primarily caused by Hepatitis C virus (HCV) infection, affects over 2.9% of the population nationwide, with regional variations. Steatotic liver disease is rapidly emerging as a significant contributor to CLD, especially in urban areas. Acid-related disorders are another widespread condition that can significantly impact the quality of life. These factors and others significantly influence the indications and findings of gastrointestinal endoscopic procedures performed in Egypt. AIM: We aimed to evaluate the clinico-demographic data, indications, and endoscopic findings in Egyptian patients undergoing gastrointestinal endoscopic procedures in various regions of Egypt. METHODS: This study employed a retrospective multicenter cross-sectional design. Data was collected from patients referred for gastrointestinal endoscopy across 15 tertiary gastrointestinal endoscopy units in various governorates throughout Egypt. RESULTS: 5910 patients aged 38-63 were enrolled in the study; 75% underwent esophagogastroduodenoscopy (EGD), while 25% underwent a colonoscopy. In all studied patients, the most frequent indications for EGD were dyspepsia (19.5%), followed by hematemesis (19.06%), and melena (17.07%). The final EGD diagnoses for the recruited patients were portal hypertension-related sequelae (60.3%), followed by acid-related diseases (55%), while 10.44% of patients had a normally apparent endoscopy. Male gender, old age, and the presence of chronic liver diseases were more common in patients from upper than lower Egypt governorates. Hematochezia (38.11%) was the most reported indication for colonoscopy, followed by anemia of unknown origin (25.11%). IBD and hemorrhoids (22.34% and 21.86%, respectively) were the most prevalent diagnoses among studied patients, while normal colonoscopy findings were encountered in 18.21% of them. CONCLUSION: This is the largest study describing the situation of endoscopic procedures in Egypt. our study highlights the significant impact of regional variations in disease burden on the utilization and outcomes of GI endoscopy in Egypt. The high prevalence of chronic liver disease is reflected in the EGD findings, while the colonoscopy results suggest a potential need for increased awareness of colorectal diseases.

LCMS-Metabolomic Profiling and Genome Mining of Delftia lacustris DSM 21246 Revealed Lipophilic Delftibactin Metallophores.

Bacteria have evolved various strategies to combat heavy metal stress, including the secretion of small molecules, known as metallophores. These molecules hold a potential role in the mitigation of toxic metal contamination from the environment (bioremediation). Herein, we employed combined comparative metabolomic and genomic analyses to study the metallophores excreted by Delftia lacustris DSM 21246. LCMS-metabolomic analysis of this bacterium cultured under iron limitation led to a suite of lipophilic metallophores exclusively secreted in response to iron starvation. Additionally, we conducted genome sequencing of the DSM 21246 strain using nanopore sequencing technology and employed antiSMASH to mine the genome, leading to the identification of a biosynthetic gene cluster (BGC) matching the known BGC responsible for delftibactin A production. The isolated suite of amphiphilic metallophores, termed delftibactins C-F (1-4), was characterized using various chromatographic, spectroscopic, and bioinformatic techniques. The planar structure of these compounds was elucidated through 1D and 2D NMR analyses, as well as LCMS/MS-based fragmentation studies. Notably, their structures differed from previously known delftibactins due to the presence of a lipid tail. Marfey's and bioinformatic analyses were employed to determine the absolute configuration of the peptide scaffold. Delftibactin A, a previously identified metallophore, has exhibited a gold biomineralizing property; compound 1 was tested for and also demonstrated this property.

Ameliorative potential of rosmarinic acid in a rat model of polycystic ovary syndrome: Targeting MCP-1 and VEGF: A histological, immunohistochemical, and biochemical study.

Polycystic ovary syndrome (PCOS) is a multidisciplinary endocrinopathy that affects women of reproductive age. It is characterized by menstrual complications, hyperandrogenism, insulin resistance, and cardiovascular issues. The current research investigated the efficacy of rosmarinic acid in letrozole-induced PCOS in adult female rats as well as the potential underlying molecular mechanisms. Forty female rats were divided into the control group, the rosmarinic acid group (50 mg/kg per orally, po) for 21 days, PCOS group; PCOS was induced by administration of letrozole (1 mg/kg po) for 21 days, and rosmarinic acid-PCOS group, received rosmarinic acid after PCOS induction. PCOS resulted in a marked elevation in both serum luteinizing hormone (LH) and testosterone levels and LH/follicle-stimulating hormone ratio with a marked reduction in serum estradiol and progesterone levels. A marked rise in tumor necrosis factor-α (TNF-α), interleukin-1ß, monocyte chemotactic protein-1, and vascular endothelial growth factor (messenger RNA) in the ovarian tissue was reported. The histological analysis displayed multiple cystic follicles in the ovarian cortex with markedly thin granulosa cell layer, vacuolated granulosa and theca cell layers, and desquamated granulosa cells. Upregulation in the immune expression of TNF-α and caspase-3 was demonstrated in the ovarian cortex. Interestingly, rosmarinic acid ameliorated the biochemical and histopathological changes. In conclusion, rosmarinic acid ameliorates letrozole-induced PCOS through its anti-inflammatory and antiangiogenesis effects.

Effects of life-story review on quality of life, depression, and life satisfaction in older adults in Oman: a randomized controlled study.

BACKGROUND: There is a need for healthcare providers to develop life-story review interventions to enhance the mental well-being and quality of life of older adults. The primary aim of this study is to examine the effects of telling their life stories and creating a life-story book intervention on QoL, depressive symptoms, and life satisfaction in a group of older adults in Oman. METHODS: A repeated-measures randomized controlled design was conducted in Oman. A total of 75 older adults (response rate = 40.1%) were randomly assigned to the intervention (n = 38) or control (n = 37) groups. Demographic data were collected as the baseline. Depression, life satisfaction, and quality of life scores were collected from each participant at weeks 1, 2, 3, 4, and 8. RESULTS: Their average age is 67.3 ± 5.5 years (range 60-82 years). There are more women (n = 50, 66.7%) than men. Over the 8 weeks, the intervention group exhibited a notable decrease in depression (intervention: 2.5 ± 1.2 vs. control: 5.3 ± 2.1, p < .001) but an increase in life satisfaction (24.6 ± 3.1 vs. 21.9 ± 6.1, p < .001) and quality of life (physical: 76.2 ± 12.7 vs. 53.6 ± 15.5, p < .001; psychological: 76.4 ± 12.1 vs. 59.9 ± 21.5, p < .001; Social relation: 78.3 ± 11.7 vs. 61.8 ± 16.6, p < .001; environment: 70.8 ± 10.2 vs. 58.6 ± 16.1, p < .001) compared to the control group. CONCLUSION: The life-story review intervention proved effective in diminishing depression and boosting life satisfaction and quality of life among the older sample within the 8-week study. Healthcare providers can apply such interventions to improve older adults' mental health and well-being.

Ameliorative Potential of Bone Marrow-Derived Mesenchymal Stem Cells Versus Prednisolone in a Rat Model of Lung Fibrosis: A Histological, Immunohistochemical, and Biochemical Study.

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease of unknown origin with limited treatment options and poor prognosis. The encouraging findings from preclinical investigations utilizing mesenchymal stem cells (MSCs) indicated that they could serve as a promising therapeutic alternative for managing chronic lung conditions, such as IPF. The objective of this study was to compare the efficiency of bone marrow-derived MSCs (BM-MSCs) versus prednisolone, the standard anti-inflammatory medication, in rats with bleomycin (BLM)-induced lung fibrosis. Four groups were created: a control group, a BLM group, a prednisolone-treated group, and a BM-MSCs-treated group. To induce lung fibrosis, 5 mg/kg of BLM was administered intratracheally. BLM significantly increased serum levels of pro-inflammatory cytokines and oxidative stress markers. The disturbed lung structure was also revealed by light and transmission electron microscopic studies. Upregulation in the immune expression of alpha-smooth muscle actin, transforming growth factor beta-1, and Bax was demonstrated. Interestingly, all findings significantly regressed on treatment with prednisolone and BM-MSCs. However, treatment with BM-MSCs showed better results than with prednisolone. In conclusion, BM-MSCs could be a promising approach for managing lung fibrosis.

ENAS-B: Combining ENAS With Bayesian Optimization for Automatic Design of Optimal CNN Architectures for Breast Lesion Classification From Ultrasound Images.

Efficient Neural Architecture Search (ENAS) is a recent development in searching for optimal cell structures for Convolutional Neural Network (CNN) design. It has been successfully used in various applications including ultrasound image classification for breast lesions. However, the existing ENAS approach only optimizes cell structures rather than the whole CNN architecture nor its trainable hyperparameters. This paper presents a novel framework for automatic design of CNN architectures by combining strengths of ENAS and Bayesian Optimization in two-folds. Firstly, we use ENAS to search for optimal normal and reduction cells. Secondly, with the optimal cells and a suitable hyperparameter search space, we adopt Bayesian Optimization to find the optimal depth of the network and optimal configuration of the trainable hyperparameters. To test the validity of the proposed framework, a dataset of 1522 breast lesion ultrasound images is used for the searching and modeling. We then evaluate the robustness of the proposed approach by testing the optimized CNN model on three external datasets consisting of 727 benign and 506 malignant lesion images. We further compare the CNN model with the default ENAS-based CNN model, and then with CNN models based on the state-of-the-art architectures. The results (error rate of no more than 20.6% on internal tests and 17.3% on average of external tests) show that the proposed framework generates robust and light CNN models.

Examining the use, confidence, and barriers to follow Advanced Life Support in Obstetrics (ALSO) course guides in managing obstetric emergencies in Sudan.

BACKGROUND: The Advanced Life Support in Obstetrics (ALSO) course is a globally recognized interprofessional training program designed to assist healthcare professionals in acquiring and sustaining the necessary knowledge and skills to handle obstetric emergencies effectively. This survey aimed to assess the use, barriers, and confidence in using the ALSO course guidelines in managing obstetric emergencies in Sudan. METHODS: This descriptive cross-sectional study involved 103 physicians from the Sudan ALSO group in Sudan. A structured, close-ended questionnaire was distributed electronically to the participants. Data analysis was conducted using Statistical Package of Social Sciences Software version 26. RESULTS: More than half of the participants were specialists (54.4%). Although all respondents claimed to adhere to the ALSO guidelines for managing shoulder dystocia, a lower percentage followed them for neonatal resuscitation (75.0%) and maternal venous thrombosis management (68.9%). Only 62.1% of participants felt confident performing neonatal resuscitation. The main barriers to implementing the ALSO course guidelines were the respondents' preference for other guidelines and their belief that the guidelines were not applicable in their specific settings. CONCLUSION: The majority of participants displayed a high level of confidence, indicating a positive perception of the guide's effectiveness. However, there is room for improvement, particularly in areas such as neonatal resuscitation and forceps-assisted births, where confidence levels were lower. Addressing barriers, including the preference for other guidelines and the applicability of the guide in specific settings, is crucial to ensure widespread adoption. Refresher training programs, contextual adaptations, and the integration of guidelines may help overcome these barriers and enhance the overall implementation of the ALSO guide in managing obstetric emergencies in Sudan.

Design and fabrication of 3D-printed gastric floating tablets of captopril: effect of geometry and thermal crosslinking of polymer on floating behavior and drug release.

The present study aims to investigate the potential of the 3D printing technique to design gastroretentive floating tablets (GFTs) for modifying the drug release profile of an immediate-release tablet. A 3D-printed floating shell enclosing a captopril tablet was designed having varying number of drug-release windows. The impact of geometrical changes in the design of delivery system and thermal cross-linking of polymers were evaluated to observe the influence on floating ability and drug release. Water uptake, water insolubilization, Differential Scanning Calorimetry (DSC), and Attenuated Total Reflection-Fourier Transform Infrared Spectroscopy (ATR-FTIR) were performed to assess the degree of thermal cross-linking of polyvinyl alcohol (PVA) filament. The 3D-printed GFT9 was considered the optimized gastric floating tablet that exhibited >12 h of total floating time with zero floating lag time and successfully accomplished modified-drug release by exhibiting >80% of drug release in 8 h. The zero-order release model, with an r2 value of 0.9923, best fitted the drug release kinetic data of the GFT9, which followed a super case II drug transport mechanism with an n value of 0.95. The optimized gastric floating device (GFT9) also exhibited the highest MDT values (238.55), representing slow drug release from the system due to thermal crosslinking and the presence of a single drug-releasing window in the device.

Knowledge and attitudes of primary care nurses towards geriatric depression in Jazan Region, Saudi Arabia.

Depression is a global health concern, particularly in the geriatric population. The increasing number of hospital admissions among older individuals highlights the need for healthcare professionals, particularly nurses, to understand and treat geriatric depression. Nurses play a crucial role in caring for older adults with depressive symptoms or depression. This study aimed to assess knowledge and attitudes regarding geriatric depression among primary care nurses in Jazan Region, Saudi Arabia. A cross-sectional study was conducted among 210 primary healthcare nurses in Jazan City using a validated self-administered questionnaire. Knowledge scores were measured and compared among selected demographic variables as well as attitudes toward geriatric depression. Data obtained were analyzed using the Statistical Package for the Social Sciences, version. 20.0. Chi-square test, fisher's exact test were used for comparison of variables with categorical data. Most primary care nurses were interested in caring for older patients with depression; however, they never attended training courses focused on geriatric depression. Where the study indicated that 38.1% of participants have poor knowledge about geriatric depression while 25.2% have good knowledge. Where the majority had a high understanding of the potential side effects of antidepressant medications, while they had limited knowledge about symptoms, diagnosis, and medications, the majority of participants demonstrated a positive attitude regarding feeling comfortable dealing with depressed patients' needs (56.7%) and considered their profession as a well-placed to assist patients (83.3%) However, 15.2% had a negative attitude citing a lack of self-discipline and willpower.

La dépression est un problème de santé mondial, en particulier dans la population gériatrique. Le nombre croissant d'hospitalisations chez les personnes âgées met en évidence la nécessité pour les professionnels de santé, en particulier les infirmières, de comprendre et de traiter la dépression gériatrique. Les infirmières jouent un rôle crucial dans la prise en charge des personnes âgées présentant des symptômes dépressifs ou une dépression. Cette étude visait à évaluer les connaissances et les attitudes concernant la dépression gériatrique parmi les infirmières de soins primaires de la région de Jazan, en Arabie Saoudite. Une étude transversale a été menée auprès de 210 infirmières de soins primaires de la ville de Jazan à l'aide d'un questionnaire auto-administré validé. Les scores de connaissances ont été mesurés et comparés parmi certaines variables démographiques ainsi que les attitudes à l'égard de la dépression gériatrique. Les données obtenues ont été analysées à l'aide du progiciel statistique pour les sciences sociales, version. 20,0. Le test du Chi carré et le test exact de Fisher ont été utilisés pour comparer les variables avec les données catégorielles. La plupart des infirmières de soins primaires souhaitaient soigner des patients âgés souffrant de dépression ; cependant, ils n'ont jamais suivi de formation axée sur la dépression gériatrique. L'étude indique que 38,1 % des participants ont de mauvaises connaissances sur la dépression gériatrique tandis que 25,2 % ont de bonnes connaissances. Alors que la majorité des participants avaient une bonne compréhension des effets secondaires potentiels des médicaments antidépresseurs, alors qu'ils avaient une connaissance limitée des symptômes, du diagnostic et des médicaments, la majorité des participants ont démontré une attitude positive et se sentaient à l'aise pour répondre aux besoins des patients déprimés (56,7 %). et considéraient leur profession comme bien placée pour assister les patients (83,3 %). Toutefois, 15,2 % avaient une attitude négative citant un manque d'autodiscipline et de volonté.

Redescription of three pinworms of the genus Cephalobellus Cobb, 1920 (Nematoda: Oxyuridomorpha: Thelastomatidae) from scarab beetle grubs from Hungary.

Larvae of European rose chafer Cetonia aurata (Linnaeus, 1758) and cockchafer Melolontha sp. beetles were collected in Hungary for parasitological study. Intestinal examination revealed the presence of three well-known thelastomatid nematodes belonging to the genus Cephalobellus Cobb, 1920. We report for the first-time Cephalobellus cuspidatum (Rudolphi, 1814) Leibersperger, 1960, C. osmodermae Leibersperger, 1960, and C. potosiae Leibersperger, 1960 in Hungary, all found in scarab beetle larvae. Due to incomplete original descriptions, a comprehensive redescription with detailed morphological data is presented. Additionally, an identification key for closely related Cephalobellus, Thelastoma and Severianoia species infesting scarab beetles worldwide is provided. Newly generated 18S and 28S rDNA gene sequences of C. osmodermae place it as one of the early branches within Thelastomatidae.

Difficulties and Challenges of EFL Simultaneous Interpretation Among Saudi Undergraduates.

Many Saudi interpretation students have challenges and difficulties during the study of simultaneous interpreting courses. Most Saudi students encounter interpretation difficulties due to inadequate training and the adoption of traditional teaching methods. This study aimed to investigate the challenges and difficulties that undergraduate simultaneous interpretation students in Saudi Arabia encountered and suggested the best solutions to address this issue. The study followed a mixed-method research design of quantitative and qualitative data collection and analysis methods to answer the research questions. The study sample was randomly selected from two Saudi universities (Najran University and King Abdul-Aziz University). Two research tools were used: a close-ended questionnaire for interpretation students and a semi-structured interview for translation professors. Responses to the questionnaire indicated that interpretation students face diverse challenges in language, curriculum, methodology, and training. Language difficulties encompassed struggles with interpreting terminology, handling long sentences, and keeping up with fast speech. Challenges related to curricula included issues of density, lack of clarity, and outdated simultaneous interpretation textbooks. Teaching method challenges were characterized by insufficient intensive training and a lack of technology-based interactive strategies. Interviews with professors highlighted additional challenges perceived by students, such as low proficiency and lack of motivation, expertise, background knowledge, equipment and labs. Professors recommended the following solutions: incorporating more practical and interactive interpretation activities, updating curricular content, offering skill-based training, and adopting modern interpretation techniques, equipment, and labs.

Development and evaluation of sildenafil/glycyrrhizin-loaded nanofibers as a potential novel buccal delivery system for erectile dysfunction.

Erectile dysfunction (ED) is a growing health condition that needs safe and effective therapy. One of the main common treatments is sildenafil which is used in clinics for managing erectile dysfunction by enhancing the blood supply to the penis. In the current study, sildenafil was formulated as nanofibers and mixed with the root extract of Glycyrrhiza glabra (glycyrrhizin) as a natural sweetener to be administrated in the buccal cavity for enhanced drug bioavailability, rapid drug absorption and improved patient compliance. The formulated dual-loaded nanofibers were evaluated by measuring diameter, disintegration, drug loading efficiency, drug release profile, and in vitro cell viability assessment. The results showed that the sildenafil/glycyrrhizin-loaded fibers had a diameter of 0.719 ± 0.177 µm and lacked any beads and pores formation on their surfaces. The drug loading and encapsulation efficiency for sildenafil were measured as 52 ± 7 µg/mg and 67 ± 9 %, respectively, while they were 290 ± 32 µg/mg and 94 ± 10 %, respectively, for glycyrrhizin. The release rate of sildenafil and glycyrrhizin demonstrated a burst release in the first minute, followed by a gradual increment until a complete release after 120 min. The in vitro cell viability evaluation exhibited that the application of sildenafil and glycyrrhizin is safe upon 24-hour treatment on human skin fibroblast cells at all used concentrations (i.e., ≤ 1,000 and 4,000 µg/mL, respectively). However, the application of sildenafil-glycyrrhizin combination (in a ratio of 1:4) demonstrated more than 80 % cell viability at concentrations of ≤ 250 and 1000 µg/mL, respectively, following 24-hour cell exposure. Therefore, sildenafil/glycyrrhizin dual-loaded PVP nanofibers showed a potential buccal therapeutic approach for erectile dysfunction management.

Nutritional and toxicological assessment of Piliostigma thonnigii leaves and Tubaani food samples: a preliminary investigation.

Tubaani is a local delicacy prepared with Piliostigma thonningii leaves. The leaves may contain trace/heavy metals and important phytonutrients that could impact consumers' health. Concerns over the nutritional and toxicological implications of Piliostigma thonningii leaves are critical. Tubaani food and Piliostigma thonningii leaf samples were investigated using Neutron Activation Analysis (NAA) and Spectrophotometry technique. The health risk of Tubaani was also assessed by calculating the target hazard quotient (THQ) and hazard index (HI) of potentially toxic elements. Fifteen trace elements were detected at non-toxicological concentrations in the samples analyzed. No significant difference (p > 0.05) was observed between the samples' mean concentrations. The phenolic content in leaf extracts was higher as compared to the flavonoids. However, the flavonoids in the leaves had an effect on the food samples, unlike the phenols. The THQ and HI of the elements were below 1.0. There is no reason to be concerned about the current dietary intake of the potentially toxic elements in the routine consumption of Tubaani as portrayed in data obtained in this investigation by NAA, THQ, and HI.

The connection between hypertension and diabetes and their role in heart and kidney disease development.

Hypertension and diabetes are two common metabolic disorders that often coexist in the same individual. Their concurrence increases the risk of cardiovascular disease, renal dysfunction, and other complications. Cardiovascular disease is the primary cause of morbidity and mortality in individuals with diabetes, and hypertension further aggravates this condition. Interestingly, hypertension and diabetes share several common pathophysiological mechanisms including insulin resistance, vascular inflammation, endothelial dysfunction, obesity, and oxidative stress suggesting a cross-talk between these two conditions that could potentially contribute to the development of other human diseases. Effective management of diabetes should include a multifaceted approach that addresses not only glycemic control but also blood pressure (BP) and lipid control. Treatment plans should be individualized to each patient's needs and should involve a combination of lifestyle modifications and medications to achieve optimal control. With the availability of newer antidiabetic medications such as SGLT inhibitors and GLP1 receptor agonists, it is crucial to consider their potential to reduce BP, enhance kidney function, and lower the risk of cardiovascular diseases when initiating treatment for glycemic control. A more profound comprehension of the shared underlying mechanisms between these conditions could pave the way for the development of innovative therapeutic approaches to tackle them. Our review offers an in-depth analysis of the literature, providing a holistic view of the mechanisms underlying diabetes-hypertension comorbidity and its implications on heart and kidney diseases. The present article concludes by discussing current approaches for managing hypertensive diabetic patients to create a set of comprehensive individualized recommendations.

Advancements in nanoparticle-based treatment approaches for skin cancer therapy.

Skin cancer has emerged as the fifth most commonly reported cancer in the world, causing a burden on global health and the economy. The enormously rising environmental changes, industrialization, and genetic modification have further exacerbated skin cancer statistics. Current treatment modalities such as surgery, radiotherapy, conventional chemotherapy, targeted therapy, and immunotherapy are facing several issues related to cost, toxicity, and bioavailability thereby leading to declined anti-skin cancer therapeutic efficacy and poor patient compliance. In the context of overcoming this limitation, several nanotechnological advancements have been witnessed so far. Among various nanomaterials, nanoparticles have endowed exorbitant advantages by acting as both therapeutic agents and drug carriers for the remarkable treatment of skin cancer. The small size and large surface area to volume ratio of nanoparticles escalate the skin tumor uptake through their leaky vasculature resulting in enhanced therapeutic efficacy. In this context, the present review provides up to date information about different types and pathology of skin cancer, followed by their current treatment modalities and associated drawbacks. Furthermore, it meticulously discusses the role of numerous inorganic, polymer, and lipid-based nanoparticles in skin cancer therapy with subsequent descriptions of their patents and clinical trials.

Unveiling the enigma of the blood-brain barrier in glioblastoma: current advances from preclinical and clinical studies.

PURPOSE OF REVIEW: Glioblastoma (GBM), the most prevalent primary brain malignancy in adults, poses significant challenges in terms of treatment. Current therapeutic strategies for GBM patients involve maximal safe resection, followed by radiotherapy with concurrent and adjuvant temozolomide. However, despite this multimodal approach for GBM, the prognosis of GBM patients remains dismal because of their inherent primary and secondary resistances to treatments. RECENT FINDINGS: Several molecular and cellular mechanisms, including the presence of the blood-brain barrier (BBB), contribute to these resistances. The BBB, comprising multiple layers surrounding brain vessels, acts as a barrier limiting effective drug delivery to the brain. Invasive and noninvasive tools to deliver drugs and pharmaceutical formulations locally or systemically are continuously evolving to overcome the BBB in GBM toward improving drug bioavailability in the brain and reducing systemic toxicities. SUMMARY: Preliminary studies utilizing these approaches have demonstrated promising results in terms of safety and signals of efficacy during early-phase clinical trials. However, further work through additional clinical trials is necessary to evaluate the potential clinical benefits for GBM patients.

Etoposide-Entrapped Progesterone-Cationic Lipid Nanoaggregates as Selective Therapeutics against Etoposide-Resistant Colorectal Cancer Cells.

Drug resistance has a major impact on the treatment of several cancers. This is mainly due to the overexpression of cellular drug efflux proteins. Hence, drug-delivery systems that can avoid this resistance are needed. We report PR10, a progesterone-cationic lipid conjugate, as a self-assembling nanoaggregate that delivers a drug cargo of etoposide, a topoisomerase inhibitor, selectively to cancer cells. In this study, we observed that etoposide nanoaggregates (P : E) caused selective and enhanced toxicity in etoposide-resistant CT26 cancer cells (IC50 9 µM) compared to when etoposide (IC50 >20 µM) was used alone. Concurrently, no toxicity was observed in etoposide-sensitive HEK293 cells for P : E treatment (IC50 >20 µM). The P : E-treated cancer cells seem to have no effect on ABCB1 expression, but etoposide-treated cells exhibited a twofold increase in ABCB1 expression, a potent efflux protein for several xenobiotic compounds. This observation supports the notion that the enhanced toxicity of P : E nanoaggregates is due to their ability to keep the expression of ABCB1 low, thus allowing longer intracellular residence of etoposide. In a BALB/c orthotopic colorectal cancer model, the nanoaggregates led to enhanced survival (45 days) compared to etoposide-treated mice (39 days). These findings suggest that PR10 could be used as a potential cancer-selective etoposide delivery vehicle to treat several etoposide-resistant cancers with fewer side effects due to the nonspecific toxicity of the drug.

Progesterone-Cationic Lipid Conjugate-Based Self-Aggregates for Cancer Cell-Selective Uptake through Macropinocytosis and the Antitumour Effect.

Progesterone (PR) is an endogenous steroid hormone that activates the progesterone receptor (PgR) and is known to play a critical role in cancer progression. Herein, we report the development of cationic lipid-conjugated PR derivatives by covalently conjugating progesterone with cationic lipids of varying hydrocarbon chain lengths (n = 6-18) through a succinate linker. Cytotoxicity studies performed on eight different cancer cell lines reveal that PR10, one of the lead derivatives, exerts notable toxicity (IC50 = 4-12 µM) in cancer cells irrespective of their PgR expression status and remains largely nontoxic to noncancerous cells. Mechanistic studies show that PR10 induces G2/M-phase cell cycle arrest in cancer cells, leading to apoptosis and cell death by inhibiting the PI3K/AKT cell survival pathway and p53 upregulation. Further, in vivo study shows that PR10 treatment significantly reduces melanoma tumor growth and prolongs the overall survival of melanoma tumor-bearing C57BL/6J mice. Interestingly, PR10 readily forms stable self-aggregates of ∼190 nm size in an aqueous environment and exhibits selective uptake into cancerous cell lines. In vitro uptake mechanism studies in various cell lines (cancerous cell lines B16F10, MCF7, PC3, and noncancerous cell line HEK293) using endocytosis inhibition proves that PR10 nanoaggregates enter selectively into the cancer cells predominantly using macropinocytosis and/or caveolae-mediated endocytosis. Overall, this study highlights the development of a self-aggregating cationic derivative of progesterone with anticancer activity, and its cancer cell-selective accumulation in nanoaggregate form holds great potential in the field of targeted drug delivery.