Sulforaphane protects against LPS-induced liver injury in mice by antagonizing oxidative stress and apoptosis through AMPK activation.

Objectives: Given the adverse effect of liver injury on a multitude of body functions, it is vital to understand its underlying mechanism and how to overcome it. In this study, lipopolysaccharide (LPS) was used to induce liver injury, while sulforaphane (SFN), a natural phytochemical, was used as the antagonist to overcome the deleterious effect. Methods: Twenty-four mice were divided into three groups: Control group (0.9% saline), LPS induction group (0.75 mg/kg), and SFN treatment (25 mg/kg) followed by LPS induction group (0.75 mg/kg), all with access to food and water ad libitum. Blood samples from retro-orbital sinus were used to measure liver function through two aminotransferases (i.e., alanine transaminase [ALT] and aspartate transaminase [AST]) whereas liver homogenate was used to measure glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) (antioxidant activity markers); caspase-3 (apoptosis marker); malondialdehyde (MDA) (lipid peroxidation marker); and NO. AMP-activated protein kinase (AMPK), a cellular energy homeostasis and lipid metabolism sensor, was also measured. Statistical analysis including normalization, analysis of variance, Kruskal-Wallis test, and significance of P < 0.05 were applied to all collected data. Results: SFN treatment significantly attenuated all tests compared to the induced liver injury by LPS where significant reduction was observed in the levels of hepatic function markers (AST and ALT), lipid peroxidation marker (MDA) as well as apoptosis marker (caspase-3) whereas a marked increase was observed for antioxidant activity markers (SOD, CAT, and GSH) and AMPK. Conclusion: These results indicate the protective effect of SFN as it re-instated the levels of antioxidation while decreasing the level of the biomarkers, which were significantly increased during liver injury induction by LPS.

Stability and performance analysis of storage root yield in a dataset of sweet potato varieties (Ipomoea batatas L.).

The dataset focuses on evaluating the performance of 17 sweet potato varieties (G) released by the Bangladesh Agricultural Research Institute (BARI) in terms of storage root yield and stability across five locations (E) in Bangladesh-Gazipur, Bogura, Jamalpur, Jashore, and Chattogram. The result revealed that BARI Mistialu-12 exhibited the highest average storage root yield at 45.35 t/ha, closely followed by BARI Mistialu-16 at 44.64 t/ha. Conversely, BARI Mistialu-1 had the lowest mean yield of 25.99 t/ha. Among the locations, Bogura recorded the highest mean root yield at 37.05 t/ha, while Chattogram exhibited the lowest at 31.27 t/ha. A combined analysis of variance revealed the presence of variability in storage root yield attributed to the genotype-location (environment) interaction (GEI). To delve deeper into this interaction, additive and multiplicative interaction effect models (AMMI) along with a linear mixed model (LMM) were employed for further investigations to confirm the significant contribution of GEI variance to root yield. The LMM results showed genetic variance (%), heritability (%), selection accuracy (%), and GEI correlation coefficients of 52.27, 54, 94, and 30, respectively. The AMMI analysis indicated that the first two principal components accounted for 74.60 % of GEI, with 20.16 % attributed to it. Assessing significant Interaction Principal Component Analyses (IPCAs) through the Weighted Average of Absolute Scores (WAAS) indicated that BARI Mistialu-12 is the most stable genotype, followed by BARI Mistialu-16 and BARI Mistialu-8, all displaying above-average root yield. The mega-environment analysis associated the highest root production of BARI Mistialu-11 and BARI Mistialu-2 with the Jamalpur location, while Gazipur, Bogura, and Jashore were linked with the superior performance of BARI Mistialu-12 and BARI Mistialu-16 genotypes. These findings are crucial for future breeding programs and the rapidly growing sweet potato industry, given the stable high-yield potential across diverse agro-ecological conditions. However, it is imperative to repeat the study to ensure reliable outcomes.

Engineered CAR-T cells targeting the non-functional P2X purinoceptor 7 (P2X7) receptor as a novel treatment for ovarian cancer.

Objectives: Recent studies have identified expression of the non-functional P2X7 (nfP2X7) receptor on various malignant cells including ovarian cancer, but not on normal cells, which makes it a promising tumour-associated antigen candidate for chimeric antigen receptor (CAR)-T-cell immunotherapies. In this study, we assessed the cytotoxic effects of nfP2X7-CAR-T cells on ovarian cancer using in vitro and in vivo models. Methods: We evaluated the effects of nfP2X7-CAR-T cells on ovarian cancer cell lines (SKOV-3, OVCAR3, OVCAR5), normal peritoneal cells (LP-9) and primary serous ovarian cancer cells derived from patient ascites in vitro using monolayer and 3D spheroid assays. We also evaluated the effects of nfP2X7-CAR-T cells on patient-derived tissue explants, which recapitulate an intact tumour microenvironment. In addition, we investigated the effect of nfP2X7-CAR-T cells in vivo using the OVCAR-3 xenograft model in NOD-scid IL2Rγnull (NSG) mice. Results: Our study found that nfP2X7-CAR-T cells were cytotoxic and significantly inhibited survival of OVCAR3, OVCAR5 and primary serous ovarian cancer cells compared with un-transduced CD3+ T cells in vitro. However, no significant effects of nfP2X7-CAR-T cells were observed for SKOV3 or normal peritoneal cells (LP-9) cells with low P2X7 receptor expression. Treatment with nfP2X7-CAR-T cells increased apoptosis compared with un-transduced T cells in patient-derived explants and correlated with CD3 positivity. Treatment with nfP2X7-CAR-T cells significantly reduced OVCAR3 tumour burden in mice compared with un-transduced CD3 cells for 7-8 weeks. Conclusion: This study demonstrates that nfP2X7-CAR-T cells have great potential to be developed as a novel immunotherapy for ovarian cancer.

Melatonin mitigates cisplatin-induced cognitive impairment in rats and improves hippocampal dendritic spine density.

Cisplatin-induced cognitive impairment (chemobrain) affects a considerable percentage of cancer patients and has no established pharmacological treatment. Chemobrain can be associated with neuroinflammation and oxidative stress. Melatonin, a pineal hormone, is known to have antioxidant, anti-inflammatory and neuroprotective potential. In this study, we investigated cisplatin-induced cognitive impairment in rats and whether melatonin can improve or reverse this impairment. Behavioral testing involved measuring working memory using the novel location recognition test (NLRT) under conditions of cisplatin or cisplatin + melatonin treatment, followed by the collection of rats' brains. The brains were subsequently stained with Golgi-Cox stain and then the hippocampus area CA3 of each one was examined, and dendritic spine density was calculated. Treatment with cisplatin resulted in deficits in the rats' performance in the NLRT (P < 0.05). These deficits were prevented by the coadministration of melatonin (P < 0.05). Cisplatin also reduced the density of dendritic spines in the hippocampus (P < 0.0001), specifically CA3 area, while the coadministration of melatonin significantly reversed this reduction (P < 0.001). This study showed that melatonin can ameliorate cisplatin-induced spatial memory deficits and dendritic spines density abnormalities in rats. Given that melatonin is a safe and wildly used supplement, it is feasible to explore its use as a palliative intervention in cancer treatment.

Monoclonal antibodies in neuro-ophthalmology.

Neuro-ophthalmologic diseases include a broad range of disorders affecting the afferent and efferent visual pathways. Recently, monoclonal antibody (mAb) therapies have emerged as a promising targeted approach in the management of several of these complex conditions. Here, we describe the mechanism-specific applications and advancements in neuro-ophthalmologic mAb therapies. The application of mAbs in neuro-ophthalmologic diseases highlights our increasing understanding of disease-specific mechanisms in autoimmune conditions such as neuromyelitis optica, thyroid eye disease, and myasthenia gravis. Due to the specificity of mAb therapies, applications in neuro-ophthalmologic diseases have yielded exceptional clinical outcomes, including both reduced rate of relapse and progression to disability, visual function preservation, and quality of life improvement. These advancements have not only expanded the range of treatable neuro-ophthalmologic diseases but also reduced adverse events and increased the response rate to treatment. Further research into neuro-ophthalmologic disease mechanisms will provide accurate and specific targeting of important disease mediators through applications of future mAbs. As our understanding of these diseases and the relevant therapeutic targets evolve, we will continue to build on our understanding of how mAbs interfere with disease pathogenesis, and how these changes improve clinical outcomes and quality of life for patients.

National Football League Game Officials Self-Rating of Knowledge in Neuro-Ophthalmic Principles and Practice: A Pilot Program to Improve Precision and Accuracy of Game Official Calls.

BACKGROUND: To determine whether a neuro-ophthalmic curriculum would improve National Football League (NFL) game officials' self-rated knowledge and interest in neuro-ophthalmic principles to improve precision and accuracy of NFL play-calling. METHODS: The formalized and structured neuro-ophthalmic principles (NOP) curriculum was introduced to 121 NFL game officials, 17 replay officials, and 4 officiating staff who attended the NFL Official Training Camp in Irving, Texas, on September 8 and 9, 2023. Before and after the lecture and videos were introduced, participants completed an optional hard-copy feedback form pertaining to self-reported NOP knowledge, likelihood of using said terms, and interest in future content of NOP applicable NFL officiating. Paired 2-tailed t tests were used for statistical analysis to directly compare the self-reported knowledge before and after the neuro-ophthalmic curriculum introduction. RESULTS: One hundred forty-two participants completed the prelecture and postlecture feedback forms self-reported knowledge after the NOP curriculum was given to the NFL officiating staff. All (142/142) participants completed a survey. There was a statistically significant improvement in the mean ratings of the prelecture vs. postlecture understanding of the specific neuro-ophthalmic terms pertinent to NFL game officials (2.6 [95% CI, 2.3-3.0] vs. 7.9 [95% CI, 7.6-8.2], P < 0.001) and 2.7 [95% CI, 2.3-3.0] vs. 7.7 [95% CI, 7.4-8.0]), respectively. There was a statistically significant greater likelihood of using said terms prelecture vs. postlecture (2.9 [95% CI, 2.4-3.4] vs. 7.5 [95% CI, 7.2-7.9], P < 0.001). CONCLUSIONS: This study found a statistically significant improvement in neuro-ophthalmic knowledge and a greater likelihood of using NOP terms following the NOP curriculum. NFL game officials, replay officials, and staff are interested in expanding their knowledge in the vision science of neuro-ophthalmic concepts and applications involved in play-calling. We hope that our pilot data will lead to a model of education that will improve the precision and accuracy of NFL play-calls by officials on game days.

Vascular Ehlers-Danlos Syndrome: A Comprehensive Natural History Study in a Dutch National Cohort of 142 Patients.

BACKGROUND: Vascular Ehlers-Danlos syndrome (vEDS) is a rare connective tissue disorder with a high risk for arterial, bowel, and uterine rupture, caused by heterozygous pathogenic variants in COL3A1. The aim of this cohort study is to provide further insights into the natural history of vEDS and describe genotype-phenotype correlations in a Dutch multicenter cohort to optimize patient care and increase awareness of the disease. METHODS: Individuals with vEDS throughout the Netherlands were included. The phenotype was charted by retrospective analysis of molecular and clinical data, combined with a one-time physical examination. RESULTS: A total of 142 individuals (50% female) participated the study, including 46 index patients (32%). The overall median age at genetic diagnosis was 41.0 years. More than half of the index patients (54.3%) and relatives (53.1%) had a physical appearance highly suggestive of vEDS. In these individuals, major events were not more frequent (P=0.90), but occurred at a younger age (P=0.01). A major event occurred more often and at a younger age in men compared with women (P<0.001 and P=0.004, respectively). Aortic aneurysms (P=0.003) and pneumothoraces (P=0.029) were more frequent in men. Aortic dissection was more frequent in individuals with a COL3A1 variant in the first quarter of the collagen helical domain (P=0.03). CONCLUSIONS: Male sex, type and location of the COL3A1 variant, and physical appearance highly suggestive of vEDS are risk factors for the occurrence and/or early age of onset of major events. This national multicenter cohort study of Dutch individuals with vEDS provides a valuable basis for improving guidelines for the diagnosing, follow-up, and treatment of individuals with vEDS.

Evaluation of Sexual Dimorphism Using Dental Dimensions - An Observational Study.

Aim: In our study, we evaluated the gender dimorphism among dental measurements of selected people in a South Indian district. Methodology: In our research, 500 participants between 17 and 25 years of age were included after taking their maxillary arch impressions. Utilizing Korkhaus compass and digital caliper, depth of palatal area as well as maxillary arch as a whole was done. T-test was done to initiate the comparative analysis between the palatal arch and complete maxillary arch depths where P < 0.05 was denoted significant statistically. Results: It was recorded that complete maxillary arch depth measurements were increased in case of men as compared to women, whereas the measurements related to depth of the palatal arch were not statistically significant. Conclusion: In our research, we found that complete maxillary arch depth can be utilized for gender segregation accompanied with other auxiliary methods. The mean value for both these measurements can be utilized as a standard measurement for advance research.

Functionalization of 68Ga-Radiolabeled Nanodiamonds with Octreotide Does Not Improve Tumor-Targeting Capabilities.

Nanodiamonds (NDs) are emerging as a novel nanoparticle class with growing interest in medical applications. The surface coating of NDs can be modified by attaching binding ligands or imaging probes, turning them into multi-modal targeting agents. In this investigation, we assessed the targeting efficacy of octreotide-functionalized 68Ga-radiolabelled NDs for cancer imaging and compared it with the tumor uptake using [68Ga]Ga-DOTA-TOC. In vivo studies in mice bearing AR42J tumors demonstrated the highest accumulation of the radiolabeled functionalized NDs in the liver and spleen, with relatively low tumor uptake compared to [68Ga]Ga-DOTA-TOC. Our findings suggest that, within the scope of this study, functionalization did not enhance the tumor-targeting capabilities of NDs.

Manufacturing of PEEK orthodontic baseplate and 3D-printed alloy components from an intraoral scan.

This paper demonstrates a digital manufacturing technique of a removable orthodontic appliance from an intraoral scan. An intraoral scan was made for the maxillary and mandibular arches. 3Shape Orthodontics Appliance Designer produced the virtual Hawley retainer, consisting of alloy components (Adam Clasps and Fitted Labial bow) and a base plate. The base plate design was modified to adapt to inserting the alloy components, which were combined using cold-cured acrylic. The finished Hawley retainer was assessed intraorally. The described technique emphasizes the design specifications of digitally designed and manufactured removable orthodontic appliances. A combination of additive and subtractive techniques was successfully employed to manufacture the alloy components and base plate. This novel method provides an alternative approach to manufacturing removable appliances with computer-aided design (CAD)/computer-aided manufacturing (CAM) technologies. The described process offers a precursor to digital manufacturing of other developed designs of dental appliances.

Transient Monocular Visual Loss (Amaurosis Fugax): How Does Age Impact Diagnosis?

Transient monocular visual loss (TMVL), also known as transient monocular blindness or amaurosis fugax ("fleeting blindness"), is a temporary loss of vision often due to ischemia to the retina. While acute TMVL should be considered an emergency that further requires exhaustive investigation, there are some cases in which TMVL arises secondary to benign causes. Age has a major impact in the diagnosis of ischemia and although the differential diagnosis of TMVL can be broad, timely and appropriate history, examination, diagnostic testing, and treatment can be vision- or life-saving. We review the causes of TMVL and the impact of age on the differential diagnoses and management.

Unlocking the Potential of Cellular Guidance in Endodontics: Advancing the Process of Pulp Regeneration and Beyond.

Regenerative endodontics represents a paradigm shift in dental therapy, with the potential to not only restore damaged dental tissues but also to preserve the vitality of teeth. At the heart of this innovative approach is cell homing, a technique that harnesses the body's own healing mechanisms by recruiting endogenous stem cells to the site of dental injury for effective tissue regeneration. This review delves into the intricate processes of cell homing in the context of regenerative endodontics, particularly focusing on its application in immature teeth with open apices. It examines the role of bioactive molecules, scaffolds, and growth factors in orchestrating cell migration and differentiation within the root canal space. In addition, the review addresses the current limitations in clinical practice, such as the challenges in completely regenerating the pulp-dentin complex and the unpredictability in long-term outcomes. It also explores future possibilities, including the potential for more refined and effective regenerative strategies. By providing a comprehensive overview of the current state of cell homing in regenerative endodontics, this article aims to contribute to the ongoing development of advanced therapeutic techniques that could revolutionize endodontic treatment and improve patient care.

Exploring the Rise of E-cigarette Use Among Male Adolescents in Al-Ahsa, Saudi Arabia: Prevalence, Patterns, and Influencing Factors.

BACKGROUND: The rising prevalence of electronic cigarette (E-cigarette) use among adolescents is a major public health concern. This study investigates the prevalence of E-cigarette use among male adolescents in Al-Ahsa, Saudi Arabia, and explores associated factors. METHODOLOGY: A cross-sectional study was conducted from December 2022 to April 2023, involving 476 male students aged 12 to 19. Data were collected through structured questionnaires, covering sociodemographic information, E-cigarette usage patterns, reasons for use, sources of acquisition, awareness of nicotine content, and perceptions of harm. Statistical analysis was performed using SPSS 25 (IBM Corp., Armonk, NY), with significance set at p < 0.05. RESULTS: The study revealed a prevalence of 17.4% E-cigarette use among participants, with 12.6% using E-cigarettes exclusively and 4.8% concurrently with traditional tobacco cigarettes. Key findings included initiation as early as age eight, sustained and frequent use, and motivations including peer influence (61.4%), curiosity (31.3%), and flavored options (26.5%). Online platforms (34.9%) and shopping malls (28.9%) were the primary sources of E-cigarette acquisition. Most participants were aware of the nicotine content (84.3%) and believed E-cigarettes were harmful (86.7%). Importantly, 69.9% expressed intentions to quit, with 44.6% planning to do so within 30 days. Significant associations were found between E-cigarette use, education level, and having friends who smoke. CONCLUSION: This study highlights the prevalence of E-cigarette use among male adolescents in Al-Ahsa, Saudi Arabia, and identifies peer influence, curiosity, and appealing flavors as driving factors. Targeted prevention and intervention programs, along with regulatory efforts to restrict access, are urgently needed to address this growing public health issue. Increasing awareness of E-cigarette risks and providing cessation support are vital steps towards mitigating E-cigarette use among Saudi male adolescents.

Long-term effectiveness of transforaminal anterolateral approach CT-guided cervical epidural steroid injections for cervical radiculopathy treatment.

AIM: To evaluate the long-term clinical effectiveness of computed tomography (CT)-guided transforaminal cervical epidural steroid injection using an anterolateral approach for the treatment of cervical radiculopathy (CR) using well-established robust clinical scoring systems for neck pain and neck disability. Despite its widespread use, evidence to support the long-term benefit of routine cervical epidural steroid injection is currently very limited. MATERIALS AND METHODS: This study included 113 patients with magnetic resonance imaging (MRI)-confirmed CR who underwent a steroid injection at a single cervical level via a unilateral transforaminal anterolateral approach. Pain was assessed quantitatively at pre-injection, 15 minutes post-injection, 1 month, 3 months, and at 1 year. Neck disability was assessed using the Oswestry Neck Disability Index (NDI) at pre-injection, 1 month, 3 months, and 1 year time points. RESULTS: Eighty patients completed the study. Sixty per cent reported reduced neck pain (mean pain reduction, 55%), which was clinically significant in 45% cases. Furthermore, 66% reported an improvement in neck disability (mean improvement, 51%), which was clinically significant for 56% patients. Clinically significant good outcomes in both neck pain and neck disability were evident from as early as 1-month, and importantly, were independent both of pre-treatment CR characteristics (including severity of pre-injection neck pain or disability) and of findings on pre-injection MRI imaging. CONCLUSION: Transforaminal anterolateral approach CT-guided epidural steroid injection resulted in a clinically significant long-term improvement in both neck pain and disability for half of the present cohort of patients with unilateral single-level CR. This improvement was independent of the severity of the initial symptoms and pre-injection MRI findings.

Cisplatin Provokes Peripheral Nociception and Neuronal Features of Therapy-Induced Senescence and Calcium Dysregulation in Rats.

Therapy-Induced Senescence (TIS) is a form of senescence that is typically described in malignant cells in response to the exposure of cancer chemotherapy or radiation but can also be precipitated in non-malignant cells. TIS has been shown to contribute to the development of several cancer therapy-related adverse effects; however, evidence on its role in mediating chemotherapy-induced neurotoxicity, such as Chemotherapy-induced Peripheral Neuropathy (CIPN), is limited. We here show that cisplatin treatment over two cycles (cumulative dose of 23 mg/kg) provoked mechanical allodynia and thermal hyperalgesia in Sprague-Dawley rats. Isolation of dorsal root ganglia (DRG) from the cisplatin-treated rats demonstrated robust SA-ß-gal upregulation at both day 8 (after the first cycle) and day 18 (after the second cycle), decreased lmnb1 expression, increased expression of cdkn1a and cdkn2a, and of several factors of the Senescence-associated Secretory Phenotype (SASP) (Il6, Il1b, and mmp9). Moreover, single-cell calcium imaging of cultured DRGs revealed a significant increase in terms of the magnitude of KCl-evoked calcium responses in cisplatin-treated rats compared to vehicle-treated rats. No significant change was observed in terms of the magnitude of capsaicin-evoked calcium responses in cisplatin-treated rats compared to vehicle-treated rats but with decreased area under the curve of the responses in cisplatin-treated rats. Further evidence to support the contribution of TIS to therapy adverse effects is required but should encourage the use of senescence-modulating agents (senotherapeutics) as novel palliative approaches to mitigate chemotherapy-induced neurotoxicity.