STA-9090 in combination with a statin exerts enhanced protective effects in rats fed a high-fat diet and exposed to diethylnitrosamine and thioacetamide.

Introduction: Liver fibrosis is a significant global health burden that lacks effective therapies. It can progress to cirrhosis and hepatocellular carcinoma (HCC). Aberrant hedgehog pathway activation is a key driver of fibrogenesis and cancer, making hedgehog inhibitors potential antifibrotic and anticancer agents. Methods: We evaluated simvastatin and STA-9090, alone and combined, in rats fed a high-fat diet (HFD) and exposed to diethylnitrosamine and thioacetamide (DENA/TAA). Simvastatin inhibits HMG-CoA reductase, depleting cellular cholesterol required for Sonic hedgehog (Shh) modification and signaling. STA-9090 directly inhibits HSP90 chaperone interactions essential for Shh function. We hypothesized combining these drugs may provide liver protective effects through complementary targeting of the hedgehog pathway. Endpoints assessed included liver function tests, oxidative stress markers, histopathology, extracellular matrix proteins, inflammatory cytokines, and hedgehog signaling components. Results: HFD and DENA/TAA caused aberrant hedgehog activation, contributing to fibrotic alterations with elevated liver enzymes, oxidative stress, dyslipidemia, inflammation, and collagen deposition. Monotherapies with simvastatin or STA-9090 improved these parameters, while the combination treatment provided further enhancements, including improved survival, near-normal liver histology, and compelling hedgehog pathway suppression. Discussion: Our findings demonstrate the enhanced protective potential of combined HMG CoA reductase and HSP90 inhibition in rats fed a HFD and exposed to DENA and TAA. This preclinical study could help translate hedgehog-targeted therapies to clinical evaluation for treating this major unmet need.

Left Middle Phalanx Tuberculous Dactylitis Masquerading as a Tumor: First Case Report in Saudi Arabia.

Tuberculous dactylitis can cause osteomyelitis, which is a rare extrapulmonary manifestation of tuberculosis, often misdiagnosed due to its nonspecific presentation and resemblance to other conditions like neoplasms. A 15-year-old male patient reported to our clinic with a 1-year history of left index finger pain and swelling following a football-related injury. Despite conservative management, the symptoms had progressively worsened over the past few months. Clinical examination revealed deformity and swelling of the middle phalanx, along with induced pain on range of motion. Bacteriological analysis indicated polymorphic nuclear cells and the presence of coagulase-negative Staphylococcus (Staphylococcus hominis). Radiographic evaluation, including x-ray and magnetic resonance imaging, revealed medullary expansion, trabecular thinning, and focal soft tissue swelling. Magnetic resonance imaging displayed extensive soft tissue and bone marrow involvement, raising concerns of a tumor. An open biopsy was performed, yielding unexpected findings of necrotizing and suppurative granulomatous inflammation, strongly suggesting an ongoing infectious process. The subsequent Quantiferon TB Gold Test confirmed tuberculosis infection. Treatment encompassed debridement, synovectomy, and initiation of an antituberculosis regimen. The patient showed significant improvement after treatment. Timely diagnosis and treatment of tuberculous dactylitis are crucial, as highlighted by the patient's positive response to combined surgical and pharmacological intervention, despite initial diagnostic challenges.

De Quervain's Tendinitis Following Trapeziectomy for the Management of Trapeziometacarpal Arthritis: A Case Report.

De Quervain's tendonitis develops when multiple factors coincide, causing the entrapment of two valuable tendons responsible for the normal range of motion of the thumb. Consequently, symptoms such as pain in the radial side of the wrist and difficulty in grasping and pinching manifest. This case report aims to discuss the presentation of De Quervain's tendinitis following trapeziectomy with suspensionplasty using the Mini TightRope implant (Arthrex, Inc., Naples, USA) for the management of trapeziometacarpal arthritis.

Phytochemical, biological, and computational investigations of Ephedra alata Decne. growing in salinity conditions of Arabian Peninsula.

Ephedra alata Decne is a medicinal plant widely used in traditional medicine for the management of bronchial asthma and cancer. Phytochemical analysis and biological activities, including antioxidant and anticancer effects, were investigated in the current work as new findings for the plant E. alata, a species growing wildly in the marsh and saline environments of the central area of Saudi Arabia. The Ultra Pressure Liquid Chromatography coupled with Electron spray ionization-Quadropole-Time of flight (UPLC-ESI-Q-TOF) system was used for the phytochemical analysis of the plant constituents. In addition, Polyphenolic profiling including the total phenolic (TPC) and flavonoid (TFC) contents of the plant extracts were measured. Phenolic acids were found at the highest relative percentages among all the identified compounds and were measured at 66.07 mg GAE (Gallic acid equivalent). The UPLC analysis of the E. alata extract indicated the presence of chlorogenic acid, syringic acid, caffeic acid, vanillic acid, rosmarinic acid, umbelliferone, isorhoifolin, and apigenin at the highest relative percentages. Mineral analysis indicated that the microelement content of E. alata was relatively low, except for magnesium (Mg). In vitro antioxidant assays revealed the ability of the plant to scavenge DPPH free radicals, reduced molybdenum ions, and ferrous at levels of 14.63, 19.97, and 27.78 mg Trolox equivalents, respectively. The extract induced transition metal chelation at 31.36 mg EDTA equivalents. The extract induced cytotoxic effects against MDA-231 and A549 cell lines at IC50 levels of 25.31 and 39.81 µg/mL, respectively. The plant extract inhibited the colonization and migration of cancer cells as part of its potential anticancer effects. In addition, major E. alata constituents like isorhoifolin, chlorogenic acid, apigenin, and rosmarinic acid exhibited the lowest binding energy to the CAIX enzyme at - 8.41, - 6.64, - 6.32, and - 6.26 kcal/mol, respectively, compared to the binding energy (- 7.72 kcal/mol) of the co-crystallized ligand (Y0R). The docking results further supported the selection of the CAIX enzyme as a standard predictive therapeutic target, since it exhibited significant binding interactions with the major constituents of the plant.

Myositis: A Rare First Presentation of Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects multiple systems with a variety of clinical manifestations and serological abnormalities. Overt myositis is a rare and not well-studied manifestation of SLE, which is associated with a more severe disease course and may be overlooked by clinicians. This case report describes a rare first presentation of SLE with myositis. An 18-year-old female patient presented with a three-month history of generalized muscle weakness, polyarthralgia, and rashes. Physical examination revealed malar rash, a dry scaly pigmented rash affecting the flanks, and a non-blanching purpuric rash with mottled discoloration and a well-defined ulceration, affecting both hands, suggestive of vasculitis. A pigmented atrophic patch on the right upper chest was also suggestive of discoid lupus. Further examination findings included bilateral upper and lower limb weakness affecting proximal muscles (Medical Research Council (MRC) grade 3/5) more than the distal muscles (MRC grade 4/5). The patient's investigation panel revealed leukopenia, anemia, elevated liver enzymes, and elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) as well as significant elevation in creatinine kinase. Further antibody testing revealed positive antinuclear antibodies (ANA), anti-double-stranded DNA (anti-dsDNA), anti-Smith, and anti-U1-ribonucleoprotein (U1RNP), along with electrodiagnostic study supporting the diagnosis of SLE complicated by myositis and vasculitis. Treatment was initiated with prednisolone, hydroxychloroquine, methotrexate, folic acid, and omeprazole with sunscreen. Over the next several months, the patient demonstrated significant clinical and laboratory improvement, regaining full muscle power, with her vasculitis rash also improving and steroid tapering initiated to avoid side effects. This case highlights the importance of recognizing myositis as a rare potential first presentation of SLE and the need for heightened clinical awareness as early diagnosis and treatment is vital for improving long-term outcomes. This case adds to the existing literature and provides a reference for future clinical encounters with such complex cases.

Efficacy of Corticosteroids for Sore Throat Management in Adults: A Systematic Review and Meta-Analysis of Randomized Trials.

Sore throat (acute pharyngitis) is among the most common complaints among adults and is a reason for seeking healthcare globally. Antibiotics are widely used among patients with infectious sore throat. Previous research has indicated that corticosteroids could offer an alternative symptomatic treatment for sore throats. To estimate the corticosteroid efficacy as an additional therapy for sore throat adult patients, the literature search included PubMed, Medline, OVID, Cochrane CENTRAL, and Scopus for articles published until July 1st, 2024. The outcomes included the onset of pain relief (average time), complete resolution of pain (average time), absolute reduction of pain at 24 and 48 hours, requirement of antibiotics, and adverse effects related to treatment. Standardized mean difference (SMD) and risk difference were used to report numerical and dichotomous results. Five studies were included. Among the five included studies, corticosteroids showed significant effectiveness in resolving pain at 24 hours (average risk difference: 0.2200, 95% CI: 0.0500 to 0.3899, p = 0.0112) but with notable heterogeneity (I² = 82.4255%). At 48 hours, the benefit was not statistically significant (average risk difference: 0.4063, 95% CI: -0.1857 to 0.9984, p = 0.1786, I² = 98.9219%). Corticosteroids also decreased the average time to onset of pain relief (average SMD: -0.6590, 95% CI: -1.2857 to -0.0323, p = 0.0393, I² = 89.7914%), although with high heterogeneity. Other findings indicated a possible reduction in antibiotic use and fewer days missed from work. Adverse effects were minimal and occurred at similar rates in both corticosteroid and placebo arms. Corticosteroids can decrease pain intensity and duration in adults with acute sore throats. However, significant heterogeneity among studies and methodological limitations render the overall evidence inconclusive. While some studies noted reduced antibiotic use and lower symptom recurrence, high-quality RCTs are needed to address these limitations and provide more definitive guidelines for corticosteroid use in treating acute pharyngitis.

The Association Between Emotional Intelligence and Academic Performance of Dental Students at King Saud University, Riyadh, Saudi Arabia.

INTRODUCTION: Emotional intelligence (EI) is reported to be associated with better academic performance. However, few studies from the Middle East have assessed whether EI affects academic performance in dental students. The objective of this study was to evaluate the relationship between EI and academic performance in a sample of Saudi Arabian dental students. METHODS: This cross-sectional, questionnaire-based study included first-year to fifth-year dental students and dental interns who were enrolled at King Saud University (KSU) in Riyadh, Saudi Arabia, for the 2023-2024 academic year. Eligible students were invited to complete the self-administered Schutte Self-Report Emotional Intelligence Test (SSEIT) and a demographic questionnaire between October 2023 and January 2024. Academic performance was assessed based on each student's self-reported overall current grade point average (GPA) and was dichotomized into high GPA (between 4.5 and 5) and low GPA (less than 4.5). RESULTS: Of the 437 eligible students, 330 (75.5%) completed the questionnaires. The logistic regression analysis, after sequentially adjusting for various risk factors, showed significantly better academic performance for those who had higher EI (OR=2.6, P-value=0.02). CONCLUSION: The findings of this study suggest a significant association between EI and academic success. EI is essential for improving academic performance in dental education.

Interpretable machine learning comprehensive human gait deterioration analysis.

Introduction: Gait analysis, an expanding research area, employs non-invasive sensors and machine learning techniques for a range of applications. In this study, we investigate the impact of cognitive decline conditions on gait performance, drawing connections between gait deterioration in Parkinson's Disease (PD) and healthy individuals dual tasking. Methods: We employ Explainable Artificial Intelligence (XAI) specifically Layer-Wise Relevance Propagation (LRP), in conjunction with Convolutional Neural Networks (CNN) to interpret the intricate patterns in gait dynamics influenced by cognitive loads. Results: We achieved classification accuracies of 98% F1 scores for PD dataset and 95.5% F1 scores for the combined PD dataset. Furthermore, we explore the significance of cognitive load in healthy gait analysis, resulting in robust classification accuracies of 90% ± 10% F1 scores for subject cognitive load verification. Our findings reveal significant alterations in gait parameters under cognitive decline conditions, highlighting the distinctive patterns associated with PD-related gait impairment and those induced by multitasking in healthy subjects. Through advanced XAI techniques (LRP), we decipher the underlying features contributing to gait changes, providing insights into specific aspects affected by cognitive decline. Discussion: Our study establishes a novel perspective on gait analysis, demonstrating the applicability of XAI in elucidating the shared characteristics of gait disturbances in PD and dual-task scenarios in healthy individuals. The interpretability offered by XAI enhances our ability to discern subtle variations in gait patterns, contributing to a more nuanced comprehension of the factors influencing gait dynamics in PD and dual-task conditions, emphasizing the role of XAI in unraveling the intricacies of gait control.

Modulating the HSP90 control over NFκB/NLRP3/Caspase-1 axis is a new therapeutic target in the management of liver fibrosis: Insights into the role of TAS-116 (Pimitespib).

Aberrant activation of the NLRP3 inflammasome is recognized to induce a chronic inflammatory response in the liver, ultimately leading to hepatic fibrosis. HSP90 is suggested to regulate NLRP3 activation and its downstream signaling. This study is the first to explore the potential therapeutic role of pimitespib in mitigating liver fibrosis in rats. The results of the study revealed that pimitespib effectively suppressed hepatic inflammation and fibrogenesis by modulating HSP90's control over the NFκB/NLRP3/caspase-1 axis. In vitro experiments demonstrated that pimitespib reduced LDH levels and increased hepatocyte survival, whereas in vivo, it prolonged the survival of rats with hepatic fibrosis. Additionally, pimitespib exhibited improvements in the function and microscopic characteristics of rat livers. Pimitespib effectively inhibited NFκB, which serves as the priming signal for NLRP3 activation. Pimitespib's inhibitory effect on NLRP3, identified as an HSP90 client protein, plays a central role in the observed anti-fibrotic effect. The simultaneous inhibition of both priming and activation signals of NLRP3 by pimitespib led to a reduction in caspase-1 activity and subsequent suppression of the N-terminal fragment of gasdermin D, ultimately constraining hepatocyte pyroptotic cell death. These diverse effects were associated with a decrease in the transcription of inflammatory mediators IL-1ß, IL-18, and TNF-α, as well as the fibrogenic mediators TGF-ß, TIMP-1, PDGF-BB, and Col1a1. Moreover, pimitespib induced the expression of HSP70, which could further contribute to the repression of fibrosis development. In summary, our findings provide an evolutionary perspective on managing liver fibrosis, positioning pimitespib as a promising candidate for anti-inflammatory and antifibrotic therapy.

Differential Expression of Branched-Chain Aminotransferase in the Rat Ocular Tissues.

Branched-chain amino acids (BCAAs) play vital roles in metabolic and physiological processes, with their catabolism initiated by two branched-chain aminotransferase isozymes: cytosolic (BCATc) and mitochondrial (BCATm). These enzymes have tissue and cell-specific compartmentalization and are believed to shuttle metabolites between cells and tissues. Although their expression and localization have been established in most tissues, ocular tissues remain unknown. In this study, we used immunohistochemical analyses to investigate the expression and localization of BCAT enzymes in the normal eye tissues. As expected, BCATc was highly expressed in the neuronal cells of the retina, particularly in the ganglion cell layers, inner nuclear layer, and plexiform layer, with little to no expression in Müller cells. BCATc was also present in the cornea, retinal pigment epithelium (RPE), choroid, ciliary body, and iris but not in the lens. In contrast, BCATm was expressed across all ocular tissues, with strong expression in the Muller cells of the retina, the endothelial and epithelial layers of the cornea, the choroid and iris, and the epithelial cells at the lens's front. The extensive expression and distribution of BCAT isozymes in the ocular tissue, suggests that BCAA transamination is widespread in the eye, potentially aiding in metabolite transport between ocular tissues. The findings provide new insights into the physiological role of BCATs in the eye, particularly within the neuronal retina.

The Prevalence, Awareness, and Associated Risk Factors of Inguinal Hernia Among the Adult Population in Saudi Arabia.

PURPOSE: Inguinal hernias lead to several potentially fatal complications such as strangulation. Assessing the prevalence, risk factors, and beliefs of a population is essential to develop appropriate preventive strategies. This study investigated the prevalence, risk factors, and awareness of inguinal hernia in the adult population of Saudi Arabia. METHODS: This cross-sectional study enrolled 461 adults aged between 18 and 60 years after excluding those aged <18 and >60 years. This study was conducted in five regions of Saudi Arabia (north, west, central, south, and east). A pre-tested questionnaire was used to collect data on the prevalence, perception, and awareness of the participants. Multivariate regression analysis was used to identify risk factors for inguinal hernia. RESULTS: The study revealed that most participants were men n=262 (56.8%), aged between 18 and 25 years n=241 (52.3%), were single n=278 (60.3%), had a bachelor's degree n=225 (48.8%) and earned less than 50,000 Saudi Riyals annually n=285 (61.8%). Most participants resided in urban areas n=366 (79.4%) with their parents n=230 (49.9%). The prevalence of inguinal hernias in adults was low (5.2%). Our results indicated a significant association between family history of inguinal hernia, chronic cough, bronchial asthma, smoking, and inguinal hernia (p < 0.001). Young adults and undergraduates displayed significantly low awareness of inguinal hernias (p < 0.001). CONCLUSION: Family history of inguinal hernia, chronic cough, bronchial asthma, and smoking were factors associated with inguinal hernia. Low awareness levels were observed among young undergraduates, with a moderate overall level of awareness.

A Retrospective Study: Evaluating the Impact of the COVID-19 Pandemic on Inflammatory Markers in Hospitalized Patients.

BACKGROUND: The COVID-19 pandemic has had a significant impact globally, and understanding the relationship between inflammatory markers and disease progression is crucial for effective management. This retrospective study aimed to examine the association between various inflammatory markers, such as C-reactive protein (CRP), the erythrocyte sedimentation rate (ESR), lactate dehydrogenase (LDH), D-dimer, ferritin, and procalcitonin (PCT), and the characteristics of disease progression and outcomes in individuals affected by COVID-19. METHODS: This study collected raw data from 470 patients who tested positive for SARS-CoV-2 using RT-PCR. RESULTS: The logistic regression analysis revealed that elevated LDH levels were associated with male gender, ICU admission, low oxygen saturation (O2 < 93%), the need for mechanical ventilation, death, and the presence of lung infiltrates. Higher D-dimer levels were associated with older age, diabetes mellitus, cardiac disease, and low oxygen saturation. Ferritin levels were significantly associated with older age, ICU admission, low oxygen saturation, mechanical ventilation, and lung infiltrates. In contrast, CRP was only significant regarding lung infiltrates and procalcitonin levels were not significantly associated with any of the examined factors. CONCLUSION: This study highlights the importance of monitoring key inflammatory markers, such as LDH, D-dimer, and ferritin, as they are significantly associated with the severity of COVID-19 illness. These findings can inform clinical decision-making and guide the development of targeted interventions to improve patient outcomes.

Impacts of aquaculture wastewater irrigation on soil health, nutrient availability, and date palm fruit quality.

Water scarcity and droughts are among the most challenging issues worldwide, particularly in arid and semi-arid regions like Saudi Arabia. Date palm (Phoenix dactylifera L.), a major crop in Saudi Arabia, is being significantly affected by water scarcity, soil salinity, and desertification. Alternative water sources are needed to conserve freshwater resources and increase date palm production in Saudi Arabia. On the other hand, Saudi Arabia has a significant number of aquaculture farms that generate substantial amounts of wastewater, which can be utilized as an alternative source of irrigation. Therefore, this study aimed to assess the potential of aquaculture wastewater as an alternative irrigation source for date palm orchards. Aquaculture wastewater was collected from 12 different farms (Al-Kharj, Al-Muzahmiya, and Al-Qassim regions, Saudi Arabia) and its quality was analyzed. The impacts of aquaculture wastewater irrigation on soil quality, nutrient availability, nutrient status of date palm trees, and dates fruit quality were assessed in comparison to source water (freshwater) irrigation at Al-Kharj, Al-Muzahmiya, and Al-Qassim regions. The water quality analyses showed higher salinity (EC = 3.31 dSm-1) in farm Q3, while all other farms demonstrated no salinity, sodicity, or alkalinity hazards. Moreover, the aquaculture wastewater irrigation increased soil available P, K, NO3--N, and NH4+-N by 49.31%, 21.11%, 33.62%, and 52.31%, respectively, compared to source water irrigation. On average, date palm fruit weight, length, and moisture contents increased by 26%, 23%, and 43% under aquaculture wastewater irrigation compared to source water irrigation. Further, P, K, Fe, Cu, and Zn contents in date palm leaf were increased by 19.35%, 34.17%, 37.36%, 38.24%, and 45.29%, respectively, under aquaculture wastewater irrigation compared to source water irrigation. Overall, aquaculture wastewater irrigation significantly enhanced date palm plant growth, date palm fruit quality, and soil available nutrients compared to freshwater irrigation. It was concluded that aquaculture wastewater can be used as an effective irrigation source for date palm farms as it enhances soil nutrient availability, date palm growth, and date fruit yield and quality. The findings of this study suggest that aquaculture wastewater could be a viable alternative for conserving freshwater resources and increase date palm production in Saudi Arabia.

Atypical Imaging Features of an Incidentally Discovered Intracranial Meningioma: A Case Report.

Intracranial meningiomas are the most common primary brain tumors, typically presenting with well-defined imaging characteristics. This case report focuses on a 56-year-old female patient who was referred due to a history of head trauma and an incidental space-occupying finding to investigate the atypical imaging appearances of intracranial meningiomas, focusing on a specific case with distinct radiological findings. Meningiomas are commonly associated with specific radiological features, such as contrast enhancement, dural tail, and hyperostosis. However, this particular case exhibited atypical imaging characteristics that raised concerns about the underlying tumor type. In-depth analysis and subsequent histopathological examination revealed a World Health Organization (WHO) grade II atypical meningioma. This variant of meningioma demonstrated increased cellularity, nuclear atypia, and a high mitotic index, indicating more aggressive tumor behavior. The study highlights the importance of recognizing atypical imaging appearances in meningiomas, as they may indicate higher-grade tumors with a potentially different clinical course and management approach. Accurate identification of these atypical features can contribute to improved diagnostic accuracy and guide appropriate surgical decision-making for patients with intracranial meningiomas.

Metastatic Pure Choriocarcinoma Masquerading in the Gastrointestinal Tract.

This study presents a rare case of pure choriocarcinoma (PCC) with metastasis to the gastrointestinal tract in a 52-year-old male with a history of mixed germ cell tumor in remission. Despite negative oncology surveillance imaging, serum marker monitoring, and a recent colonoscopy, the patient presented with new-onset melena and dysphagia, leading to further diagnostic evaluation. Endoscopic examination revealed an ulcerated duodenal mass, and a computer tomography (CT)-guided liver biopsy confirmed metastatic PCC. This case highlights the aggressive nature of PCC and the importance of considering gastrointestinal metastasis in patients with atypical symptoms, even when in apparent remission.

The impact of study habits and personal factors on the academic achievement performances of medical students.

BACKGROUND: Academic achievement is essential for all students seeking a successful career. Studying habits and routines is crucial in achieving such an ultimate goal. OBJECTIVES: This study investigates the association between study habits, personal factors, and academic achievement, aiming to identify factors that distinguish academically successful medical students. METHODS: A cross-sectional study was conducted at the College of Medicine, King Saud University, Riyadh, Saudi Arabia. The participants consisted of 1st through 5th-year medical students, with a sample size of 336. The research team collected study data using an electronic questionnaire containing three sections: socio-demographic data, personal characteristics, and study habits. RESULTS: The study results indicated a statistically significant association between self-fulfillment as a motivation toward studying and academic achievement (p = 0.04). The results also showed a statistically significant correlation between recalling recently memorized information and academic achievement (p = 0.05). Furthermore, a statistically significant association between preferring the information to be presented in a graphical form rather than a written one and academic achievement was also found (p = 0.03). Students who were satisfied with their academic performance had 1.6 times greater chances of having a high-grade point average (OR = 1.6, p = 0.08). CONCLUSION: The results of this study support the available literature, indicating a correlation between study habits and high academic performance. Further multicenter studies are warranted to differentiate between high-achieving students and their peers using qualitative, semi-structured interviews. Educating the students about healthy study habits and enhancing their learning skills would also be of value.

Cancer-specific alterations in nuclear matrix proteins determined by multi-omics analyses of ductal carcinoma in situ.

Introduction: Breast cancer (BC) is the most common cancer affecting women in the United States. Ductal carcinoma in situ (DCIS) is the earliest identifiable pre-invasive BC lesion. Estimates show that 14 to 50% of DCIS cases progress to invasive BC. Methods: Our objective was to identify nuclear matrix proteins (NMP) with specifically altered expression in DCIS and later stages of BC compared to non-diseased breast reduction mammoplasty and a contralateral breast explant culture using mass spectrometry and RNA sequencing to accurately identify aggressive DCIS. Results: Sixty NMPs were significantly differentially expressed between the DCIS and non-diseased breast epithelium in an isogenic contralateral pair of patient-derived extended explants. Ten of the sixty showed significant mRNA expression level differences that matched the protein expression. These 10 proteins were similarly expressed in non-diseased breast reduction cells. Three NMPs (RPL7A, RPL11, RPL31) were significantly upregulated in DCIS and all other BC stages compared to the matching contralateral breast culture and an unrelated non-diseased breast reduction culture. RNA sequencing analyses showed that these three genes were increasingly upregulated with BC progression. Finally, we identified three NMPs (AHNAK, CDC37 and DNAJB1) that were significantly downregulated in DCIS and all other BC stages compared to the isogenically matched contralateral culture and the non-diseased breast reduction culture using both proteomics and RNA sequencing techniques. Discussion: These genes should form the basis of, or contribute to, a molecular diagnostic panel that could identify DCIS lesions likely to be indolent and therefore not requiring aggressive treatment.

Quorum Sensing Inhibitors: An Alternative Strategy to Win the Battle against Multidrug-Resistant (MDR) Bacteria.

Antibiotic resistance is a major problem and a major global health concern. In total, there are 16 million deaths yearly from infectious diseases, and at least 65% of infectious diseases are caused by microbial communities that proliferate through the formation of biofilms. Antibiotic overuse has resulted in the evolution of multidrug-resistant (MDR) microbial strains. As a result, there is now much more interest in non-antibiotic therapies for bacterial infections. Among these revolutionary, non-traditional medications is quorum sensing inhibitors (QSIs). Bacterial cell-to-cell communication is known as quorum sensing (QS), and it is mediated by tiny diffusible signaling molecules known as autoinducers (AIs). QS is dependent on the density of the bacterial population. QS is used by Gram-negative and Gram-positive bacteria to control a wide range of processes; in both scenarios, QS entails the synthesis, identification, and reaction to signaling chemicals, also known as auto-inducers. Since the usual processes regulated by QS are the expression of virulence factors and the creation of biofilms, QS is being investigated as an alternative solution to antibiotic resistance. Consequently, the use of QS-inhibiting agents, such as QSIs and quorum quenching (QQ) enzymes, to interfere with QS seems like a good strategy to prevent bacterial infections. This review sheds light on QS inhibition strategy and mechanisms and discusses how using this approach can aid in winning the battle against resistant bacteria.

Impact of undersampling on preclinical lung T2* mapping with 3D radial UTE MRI at 7 T.

Lung diseases are almost invariably heterogeneous and progressive, making it imperative to capture temporally and spatially explicit information to understand the disease initiation and progression. Imaging the lung with MRI-particularly in the preclinical setting-has historically been challenging because of relatively low lung tissue density, rapid cardiac and respiratory motion, and rapid transverse (T2*) relaxation. These limitations can largely be mitigated using ultrashort-echo-time (UTE) sequences, which are intrinsically robust to motion and avoid significant T2* decay. A significant disadvantage of common radial UTE sequences is that they require inefficient, center-out k-space sampling, resulting in long acquisition times relative to conventional Cartesian sequences. Therefore, pulmonary images acquired with radial UTE are often undersampled to reduce acquisition time. However, undersampling reduces image SNR, introduces image artifacts, and degrades true image resolution. The level of undersampling is further increased if offline gating techniques like retrospective gating are employed, because only a portion (∼40-50%) of the data is used in the final image reconstruction. Here, we explore the impact of undersampling on SNR and T2* mapping in mouse lung imaging using simulation and in-vivo data. Increased scatter in both metrics was noticeable at around 50% sampling. Parenchymal apparent SNR only decreased slightly (average decrease âˆ¼ 1.4) with as little as 10% sampling. Apparent T2* remained similar across undersampling levels, but it became significantly increased (p < 0.05) below 80% sampling. These trends suggest that undersampling can generate quantifiable, but moderate changes in the apparent value of T2*. Moreover, these approaches to assess the impact of undersampling are straightforward to implement and can readily be expanded to assess the quantitative impact of other MR acquisition and reconstruction parameters.

Novel embelin-loaded transniosomes for topical delivery: comprehensive exploration of in vitro, ex vivo and dermatokinetic assessment for anti-cancer activity.

BACKGROUND: This study systematically designed and optimised a transniosomal formulation containing embelin for skin cancer management. The transniosomes were developed using a rotary evaporation method and then optimised using a Box-Behnken design. RESULTS: The optimized embelin-loaded transniosomes (Opt-EMB-TNs) exhibited a vesicle size of 149.01 nm, polydispersity index of 0.184, a zeta potential of -21.14 mV, an entrapment efficiency of 75.6 ± 0.65%, drug loading of 3.36 ± 0.03% and drug release of 80.88 ± 2.55%. The antioxidant potential of Opt-EMB-TNs was found to be 88.54% when compared to standard ascorbic acid. Dermatokinetic studies showed a greater drug deposition in targeted skin areas with Opt-EMB-TN gel compared to the embelin conventional gel (EMB-CF gel). In addition, the penetration depth study of the skin sample revealed that the transniosomal gel containing rhodamine B dye exhibited higher penetration than that of the rhodamine B dye containing hydroalcoholic solution. The efficacy of Opt-EMB-TNs for skin cancer was confirmed by cytotoxicity assay against the B16F10 melanoma cell line. CONCLUSION: The study concluded that the Opt-EMB-TN gel formulation is a promising and effective topical treatment for skin cancer, demonstrating significant potential for further development and clinical application. © 2024 Society of Chemical Industry.