Sinomenine (SIN) is widely used in China to treat a variety of rheumatic diseases (RA), and has various pharmacological effects such as anti-inflammatory, analgesic, and anti-tumor effects. However, due to the histamine release characteristics of SIN, its adverse reactions such as allergic reactions, gastrointestinal reactions, and circulatory systemic reactions have been drawing increasing attention. We present here a systematic review of the chemical structure, pharmacological effects, clinical application, and adverse reactions of SIN, a detailed discussion on the relationship between histamine/histamine receptor and mechanism of action of SIN. In addition, we simulated the binding of SIN to four histamine receptors by using a virtual molecular docking method and found that the bonding intensity between SIN and receptors varied in the order shown as follows: H1R > H2R ~ H3R > H4R. The docking results suggested that SIN might exhibit dual regulatory effects in many processes such as cyclooxygenase-2 (COX-2) expression, NF-κB pathway activation, and degranulation of mast cells to release histamine, thereby exhibiting pro-inflammatory (adverse reactions)/anti-inflammatory effects. This study provides a theoretical basis for the clinical treatment of inflammations seen such as in RA using SIN, and also suggests that SIN has great potential in the field of cancer treatment and will have very important social and economic significance.

Background/Objectives: Besides a multitude of consequences patients on chronic renal replacement therapy have, anemia is one of the most prominent factors making a significant number of patients dependent on erythropoiesis-stimulating agent (ESA) therapy. The aim of this study was to examine the relationship between the levels of a broad spectrum of thrombo-inflammatory and oxidative stress-related biomarkers and the presence and level of ESA hyporesponsiveness in patients undergoing regular chronic hemodialysis. Methods: This cross-sectional study included 96 patients treated with chronic hemodialysis. Levels of several thrombo-inflammatory and oxidative stress-related biomarkers, as well as demographic, clinical, and laboratory analyses, were collected and analyzed based on the calculated value of the ESA-hyporesponsiveness index (EHRI). Results: In the analyzed sample, 58 patients received ESAs. Of all the investigated parameters, only body mass index (BMI), level of plasminogen activator inhibitor-1, and level of L-type fatty acid binding protein (L-FABP) were observed as significant predictors of EHRI. A significant diagnostic potential for ESA resistance has been observed in BMI and L-FABP between ESA-resistant and ESA-non-resistant groups of patients (p = 0.004, area under the curve 0.763 and p = 0.014, area under the curve 0.712, respectively) with the cut-off values of 25.46 kg/m² and 5355.24 ng/mL, respectively. Having a BMI of 25.46 kg/m² or less and an L-FABP level higher than 5355.24 ng/mL were observed as significant predictors of ESA resistance (odds ratio 9.857 and 6.125, respectively). Conclusions: EHRI was positively predicted by low BMI and high levels of plasminogen activator inhibitor-1 and L-FABP. High levels of L-FABP and low BMI have been observed as strong predictors of ESA resistance.

Stevens Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN) are mainly drug-induced severe cutaneous adverse reactions with increased mortality. It also involves the eyes causing ocular surface disease leading to visual impairment and blindness. The role of NLRP3 Inflammasome in causing ocular surface disease and keratinocyte apoptosis is not fully explored. This study is focused on determining the role of NLRP3 Inflammasome in the pathogenesis of SJS/TEN. The NLRP3 Inflammasome plays a crucial role in the pathogenesis of SJS/TEN and may correlate with the degree of severity of skin detachment and ocular surface disease. This study looked at the expression of the NLRP3 Inflammasome in the skin of patients with biopsy confirmed SJS/TEN compared to the lichen planus and normal controls by immunohistochemistry as well as observing the mitochondrial function of platelets challenged with plasma from patients with SJS/TEN and Normal Human Plasma using Agilent Seahorse XF Analyzer. Under a current, Loyola IRB approved protocol, 12 collected and archived unstained slides of skin and blood plasma samples from patients with biopsy confirmed SJS/TEN was used for this study. Immunohistochemical analysis was performed using anti-NLRP3 antibodies followed by imaging on a Delta Vision microscope. The precise roles of cytokines and chemokine receptors in severity of skin detachment has not been completely studied. The identification of the roles of NLRP3 in SJS/TEN would bridge the gaps in the basic understanding regarding the pathogenesis of this disease spectrum, especially skin detachment seen in SJS/TEN. NLRP3 Inflammasome is a potential therapeutic target and its inhibition by phytochemicals may be appropriate effective treatment strategies in the management of this condition.

Background/Objectives: Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis (SJS/TEN) are rare but severe skin conditions, often triggered by medications, that can be life-threatening. These conditions frequently affect the eyes, causing ocular surface disease, which can result in visual impairment or blindness. Although the exact mechanisms behind SJS/TEN remain unclear, key inflammatory mediators such as IL-1β, IL-6, and RIPK3 are believed to play critical roles in inflammation, necroptosis, and regulatory processes. Investigating these factors offers new insights into the disease’s underlying mechanisms and potential targets for treatment. This study aims to determine the roles of IL-1β, IL-6, and RIPK3 in the pathogenesis of SJS/TEN. Methods: The study examined the expression levels of IL-1β, IL-6, and RIPK3 in skin biopsies from patients with biopsy-confirmed SJS/TEN, using lichen planus as a positive control and normal skin as a baseline control. Immunohistochemistry was employed for this analysis. Additionally, the impact of SJS/TEN patient plasma on mitochondrial function was assessed in platelets and human corneal epithelial (H-CET) cells. Using a fluorescent plate reader, mitochondrial activity and superoxide ion levels were measured, comparing plasma from SJS/TEN patients to normal human plasma. Results: Skin biopsies from SJS/TEN patients showed a significantly higher expression of IL-1β, IL-6, and RIPK3 compared to both lichen planus and normal controls. Furthermore, plasma from SJS/TEN patients significantly reduced platelet viability and increased mitochondrial and total cellular superoxide ions, as demonstrated by elevated levels of MitoSOX Red and CellROX Red. Conclusions: These findings suggest that IL-1β, IL-6, and RIPK3 may contribute to the pathogenesis of SJS/TEN and highlight their potential as targets for therapeutic intervention.

This paper describes the design of a mobile based gaming application - Meri Kahani - created to teach computational thinking skills to school going teenagers in underdeveloped areas of Pakistan. We explore the use of gamification to teach computational thinking through level-based learning in a Pakistani context. This paper's final design demonstrates how gamified learning, rewarding techniques, and feminine themes can be used to attract female teenagers towards computational thinking. This paper also discusses the evaluation and usability testing results conducted on 16 school-going female teenagers. We hope that through this study, we have taken the first step towards nurturing an interest in young females for computational thinking and overcoming the gender gap that adversely affects female involvement in Computer Science in Pakistan.