To investigate brain melanin deposition on magnetic resonance imaging (MRI) in hypomelanosis of Ito (HI) by presenting two clinical cases and reviewing relevant literature. Two patients clinically diagnosed with HI underwent comprehensive neurological and systemic evaluations. Detailed MRI was performed to identify parenchymal changes suggestive of melanin deposition. A literature review was conducted to compare the imaging findings and discuss embryological and neurocutaneous correlations. Both cases presented with typical hypopigmented cutaneous lesions but without dysmorphic features. MRI of the first child revealed left hemimegalencephaly, diffuse white matter abnormalities, and multiple nodular lesions that were T2-hypointense and T1-hyperintense, suggesting possible intracranial melanosis. In contrast, MRI of the second patient demonstrated T2 hyperintensities in the juxtacortical white matter of the medial occipital lobe with blooming on susceptibility-weighted imaging sequences; however, hemimegalencephaly was absent. Histological confirmation was not possible due to lack of consent for brain biopsy. We report a rare case of probable intracranial melanin deposition in HI, inferred from characteristic MRI signal patterns. These findings may reflect aberrant melanocyte migration into the brain, consistent with their shared neural crest origin with neurons. Although histopathological verification was not feasible, our observations underscore the need for further pathological validation and exploration of the neurocutaneous interface in pigmentary disorders.

Objective: Biological processes are the sum of metabolic reactions that result in intermediate and end metabolite products. These processes are the reflection of genetic regulation and are profoundly impacted by environmental influence and changes, including those associated with attention-deficit/hyperactivity disorder (ADHD). This study aimed to assess the untargeted plasma metabolomic profile of children and adolescents with ADHD and to compare them with healthy controls and to study associations of dysregulated metabolic parameters with the clinical and socio-demographic parameters of ADHD. Methods: This study involved 42 registered cases of ADHD among children aged 6 to 16 years, diagnosed based on DSM-5 criteria. Each case was matched by age and gender with 24 healthy controls. The severity of ADHD was evaluated using the ADHD Rating Scale, while behavioral issues were assessed through the Child Behavior Checklist. The gas chromatography-mass spectrometry technique was employed to examine changes in plasma metabolite content. Results: We identified a total of 45 metabolites in the ADHD subtypes, which exhibited altered levels compared to the control group. The content of these metabolites and associated metabolic pathways showed significant differences between ADHD subjects and controls. Furthermore, we analyzed biomarkers derived from the compounds with the greatest fold changes in accumulation levels. Conclusion The identification and analysis of these metabolites and metabolic pathways represent a promising new approach for tracking disease progression in ADHD. The findings of this study indicate that metabolite-based biomarkers may hold considerable potential for effective disease management.

Isoliquiritigenin (ISL), a phenolic compound derived from licorice, exhibits various biological activities, including anti-inflammatory, anti-viral, anti-tumor, and antioxidant effects. However, the molecular mechanisms underlying its anti-cancer effects are not well understood in SK-MEL-28 melanoma cells. Melanoma, a highly aggressive and treatment-resistant cancer, remains a significant health challenge. This study investigates the anti-cancer effects of ISL, focusing on identifying reactive oxygen species (ROS)-mediated apoptosis mechanisms on SK-MEL-28 melanoma cells. Our results show that ISL treatment induces apoptosis in SK-MEL-28 cells, as evidenced by the cleavage of caspase-9, -7, -3, and PARP. ISL increased Bax expression, decreased Bcl-2 expression, and promoted cytochrome C release into the cytosol. ISL also reduced the expression of cell cycle markers, including cyclin D1, D3, and survivin. Notably, ISL treatment markedly increased intracellular ROS levels and pretreatment with N-acetyl cysteine, a ROS scavenger, abrogated the ISL-induced inhibition of the p38/mTOR/STAT3 pathway and prevented apoptosis.Moreover, ISL significantly diminished the constitutive phosphorylation of mTOR and STAT3 in SK-MEL-28 cells by blocking the phosphorylation of p38 MAPK, an upstream kinase of mTOR. Pharmacological inhibition of mTOR attenuated the STAT3 signaling, indicating that mTOR acts as an upstream kinase of STAT3 in these cells. Collectively, these findings demonstrate that ISL inhibits SK-MEL-28 cell growth by downregulating cell survival proteins and inducing apoptosis through ROS generation.

Isoliquiritigenin (ISL), a phenolic compound derived from licorice, exhibits various biological activities, including anti-inflammatory, anti-viral, anti-tumor, and antioxidant effects. However, the molecular mechanisms underlying its anti-cancer effects are not well understood in SK-MEL-28 melanoma cells. Melanoma, a highly aggressive and treatment-resistant cancer, remains a significant health challenge. This study investigates the anti-cancer effects of ISL, focusing on identifying reactive oxygen species (ROS)-mediated apoptosis mechanisms on SK-MEL-28 melanoma cells. Our results show that ISL treatment induces apoptosis in SK-MEL-28 cells, as evidenced by the cleavage of caspase-9, -7, -3, and PARP. ISL increased Bax expression, decreased Bcl-2 expression, and promoted cytochrome C release into the cytosol. ISL also reduced the expression of cell cycle markers, including cyclin D1, D3, and survivin. Notably, ISL treatment markedly increased intracellular ROS levels and pretreatment with N-acetyl cysteine, a ROS scavenger, abrogated the ISL-induced inhibition of the p38/mTOR/STAT3 pathway and prevented apoptosis.Moreover, ISL significantly diminished the constitutive phosphorylation of mTOR and STAT3 in SK-MEL-28 cells by blocking the phosphorylation of p38 MAPK, an upstream kinase of mTOR. Pharmacological inhibition of mTOR attenuated the STAT3 signaling, indicating that mTOR acts as an upstream kinase of STAT3 in these cells. Collectively, these findings demonstrate that ISL inhibits SK-MEL-28 cell growth by downregulating cell survival proteins and inducing apoptosis through ROS generation.

Isoliquiritigenin (ISL), a phenolic compound derived from licorice, exhibits various biological activities, including anti-inflammatory, anti-viral, anti-tumor, and antioxidant effects. However, the molecular mechanisms underlying its anti-cancer effects are not well understood in SK-MEL-28 melanoma cells. Melanoma, a highly aggressive and treatment-resistant cancer, remains a significant health challenge. This study investigates the anti-cancer effects of ISL, focusing on identifying reactive oxygen species (ROS)-mediated apoptosis mechanisms on SK-MEL-28 melanoma cells. Our results show that ISL treatment induces apoptosis in SK-MEL-28 cells, as evidenced by the cleavage of caspase-9, -7, -3, and PARP. ISL increased Bax expression, decreased Bcl-2 expression, and promoted cytochrome C release into the cytosol. ISL also reduced the expression of cell cycle markers, including cyclin D1, D3, and survivin. Notably, ISL treatment markedly increased intracellular ROS levels and pretreatment with N-acetyl cysteine, a ROS scavenger, abrogated the ISL-induced inhibition of the p38/mTOR/STAT3 pathway and prevented apoptosis.Moreover, ISL significantly diminished the constitutive phosphorylation of mTOR and STAT3 in SK-MEL-28 cells by blocking the phosphorylation of p38 MAPK, an upstream kinase of mTOR. Pharmacological inhibition of mTOR attenuated the STAT3 signaling, indicating that mTOR acts as an upstream kinase of STAT3 in these cells. Collectively, these findings demonstrate that ISL inhibits SK-MEL-28 cell growth by downregulating cell survival proteins and inducing apoptosis through ROS generation.

Dendritic cells (DCs) are highly efficient antigen-presenting cells located throughout body tissues and surfaces. Initial studies described these cells as potent activators of naïve T lymphocytes; however, subsequent research has demonstrated that DCs can also regulate T cell activation, survival, and effector functions. DCs possessing T cell regulatory properties, known as regulatory DCs (regDCs), are phenotypically immature cells with modified functionality. In humans, regDCs are typically derived from blood monocytes and characterized by the surface marker expression profile CD11c lo CD-11b hi CD14 + HLA-DR + , low expression of major histocompatibility complex class I molecules, adhesion proteins, and costimulatory markers (e.g., CD40, CD80), and high expression of immune checkpoint and apoptosis-inducing ligands (e.g., PD-L1, Fas ligand). Additionally, these cells secrete abundant anti-inflammatory cytokines, includ-ing interleukin-10 and transforming growth factor-β. Preclinical studies using rodentand nonhuman primate models have demonstrated the efficacy of regDCs in mitigating allograft rejection. Likewise, clinical studies evaluating regDCs have confirmed their safety, efficacy, and feasibility for inducing antigen-specific immune tolerance and/or reducing solid organ transplant rejection. In this manuscript, we review the tolerogenic potential of regDCs, the mechanisms by which regDCs mediate immune tolerance, and the findings from preclinical and clinical studies assessing their use in mitigating solid organ transplant rejection.

Background: s/Aims: Open cholecystectomy is becoming obsolete and laparoscopic cholecystectomy has become the treatment of choice in gallstone diseases. Difficult gallbladders are encountered whenever there is a frozen calot’s triangle, obliterated cystic plate, or both. Rather than converting to open procedure, there has been a growing preference for laparoscopic subtotal cholecystectomy (LSC) during difficult gallbladders. This study aimed to assess the advantages, indications, and viability of LSC in difficult gallbladders. Methods: The study included patients undergoing laparoscopic cholecystectomy in NIMS Hospital, Jaipur, from January 2021 to January 2023. Data of the patients who underwent LSC for difficult gallbladders included demographics, comorbidities, operative time, conversion to open cholecystectomy, length of hospital stay, and complications. LSC was classified into three types depending on the part of the gallbladder remnant. Results: A total of 728 patients underwent laparoscopic cholecystectomy. Among them, 41 patients (5.6%) were attempted for LSC.However, one patient was converted to an open procedure and the rest 40 underwent LSC. LSC was divided into 3 types, 4 patients underwent LSC type I, 34 patients underwent type II, and 2 patients type III. The average operating time and postoperative length of hospital stay were 86.2 minutes and 2.1 days, respectively. Two patients had surgical site infection. No patient had a bile leak and none required intensive care unit care. Conclusions LSC is a safe and feasible option for use in difficult gallbladders.

Bacillus Calmette-Guérin (BCG) is an attenuated strain of Mycobacterium bovis. Although it was developed as a prophylactic vaccine against tuberculosis (TB), researchers have also evaluated it for preventing cancer development or progression. These studies were inspired by the available data regarding the protective effects of microbial infection against cancers and an inverse relationship between TB and cancer mortality. Initial studies demonstrated the efficacy of BCG in preventing leukemia, melanoma and a few other cancers. However, mixed results were observed in later studies. Importantly, these studies have led to the successful use of BCG in the tertiary prevention of non-muscle invasive bladder cancer, wherein BCG therapy has been found to be more effective than chemotherapy. Moreover, in a recently published 60-year follow-up study, childhood BCG vaccination has been found to significantly prevent lung cancer development. In the present manuscript, we reviewed the studies evaluating the efficacy of BCG in cancer prevention and discussed its putative mechanisms. Also, we sought to explain the mixed results of BCG efficacy in preventing different cancers.

OBJECTIVES: Dengue is a mosquito-borne viral disease globally transmitted by Aedes aegypti. The most effective method to prevent the transmission of the disease is proficient vector control. Understanding the breeding behaviour of the responsible vectors is very pertinent in this regard; therefore, the present study was conducted to understand Ae. aegypti behaviour regarding the selection of containers for oviposition in the megacity of Delhi. METHODS: A household survey in different localities within Delhi was carried out during 2018-2019. All available containers were inspected for the presence of immature Ae. aegypti. In entomological surveillance, the ovipositional preference of Aedes was computed using the breeding preference ratio, container index in the field, and laboratory settings, and associations of dengue cases with monthly variation in environmental factors and container type were also calculated. RESULTS: The household larval survey in 40 localities showed that 40% of 27,776 water-holding containers in 3,400 houses were plastic, followed by overhead tanks (26.2%), and coolers (12.1%). The most preferred breeding habitat was clay pots (9.3%), followed by metallic containers (8.5%) and solid waste (7.1%). A laboratory-based study showed that Aedes preferred clay containers (81.8%) over 4 other types of containers (plastic, paper, metal, and glass). CONCLUSIONS The present study provides a rationale for using clay containers as a possible surveillance tool (ovitraps) or as a vector control tool. This information might aid researchers in developing novel traps and targeting preferred containers for larval control activities during transmission and non-transmission seasons.