This study aims to measure oxidative stress levels in cataract patients with varying causes. Total antioxidant capacity (TAC) and malondialdehyde (MDA) levels in the aqueous humor are biomarkers of oxidative stress in the eye, in which ocular comorbidities and systemic conditions will influence preexisting oxidative stress, as will the phacoemulsification surgery performed. Consequently, this study investigates the changes in MDA levels after phacoemulsification and clinical manifestations of the corneal endothelial layer after surgery. Samples from 34 subjects were collected using a consecutive sampling approach. Ethical approval was obtained from the Ethics Committee of Cipto Mangunkusumo National Referral Hospital, Faculty of Medicine, University of Indonesia (Approval No. KET-1156/UN2.F1/ETIK/PPM.00.02/2024). Aqueous humor samples were collected during and after phacoemulsification to measure MDA and TAC levels. Biomarker results were analyzed using SPSS ver. 25. A total of 34 cataract patients with various conditions were analyzed. Prephacoemulsification MDA levels were found to be not significantly different among groups categorized by nuclear density and prior surgery status. Postphacoemulsification MDA level is 58.38 ng/mL, lower insignificantly compared to pre-MDA level. However, in the postoperative analysis, MDA levels were found to have no significant correlation between cumulative dissipated energy and endothelial cell density loss (P = 0.723 and P = 0.676). Biomarker levels can vary widely among cataract cases, reflecting heterogeneous oxidative stress responses. These short-term preliminary findings suggest that surgical parameters or early endothelial outcomes may not directly predict oxidative stress responses in the aqueous humor.

Background Treatment response in acute myeloid leukemia (AML) is influenced by multiple biological and molecular mechanisms. High-mobility group box 1 (HMGB-1) is involved in inflammation, autophagy, apoptosis, and immunogenic cell death. This study evaluated associations of baseline circulating miR-181a-3p, miR-181b-5p, ATM, ATR, and HMGB-1 with successful induction response in adults with newly diagnosed AML. Methods This prospective cohort study was conducted at two referral hospitals in Jakarta, Indonesia. Adults with newly diagnosed AML receiving standard D3A7 induction chemotherapy were enrolled consecutively. Baseline miR-181a-3p and miR-181b-5p were quantified using digital polymerase chain reaction, whereas ATM, ATR, and HMGB-1 were measured using enzyme-linked immunosorbent assays before chemotherapy. Successful induction response was assessed by clinical and bone marrow evaluation after induction. Receiver operating characteristic analysis determined an exploratory HMGB-1 cut-off. Associations were evaluated using relative risks (RRs) with 95% confidence intervals (CIs). Results Among 102 patients initiating induction chemotherapy, 25 died during induction or early post-induction care. The biomarker-evaluable cohort comprised 71 patients, of whom 40 (56.3%) achieved a successful response. Baseline miR-181a-3p, miR-181b-5p, ATM, and ATR were not significantly associated with response. HMGB-1 yielded an area under the curve of 0.615 (95% CI, 0.480–0.749). The exploratory cut-off was 28.59 pg/mL, with 65.0% sensitivity and 61.3% specificity. Low HMGB-1 was associated with a lower probability of successful response (RR, 0.620; 95% CI, 0.394–0.975; p = 0.038). In the final clinical-biomolecular model, high HMGB-1 remained associated with successful response after adjustment for platelet count and ATR (adjusted RR, 1.666; 95% CI, 1.092–2.541; p = 0.018). Conclusion Low baseline circulating HMGB-1 was associated with a lower probability of successful induction response in the biomarker-evaluable adult AML cohort. Given its modest discriminatory performance and internally derived cut-off, HMGB-1 should be considered an exploratory complementary biomarker requiring external validation and serial evaluation.

Ginger (Zingiber officinale) is well known for its beneficial effects on health, and it use as a culinary spice, mainly due to the presence of bioactive compounds such as 6-,8-, and 10-gingerol. Although 6-gingerol exhibits remarkable therapeutic potential, its clinical application is constrained by poor bioavailability and rapid metabolic degradation. Nanotechnology-based drug delivery systems have been widely explored to overcome these limitations by improving the stability, solubility, and bioavailability of bioactive compounds. Among these systems, nanostructured lipid carriers (NLCs) have attracted considerable to facilitate high drug-loading, enhanced stability, and controlled drug release. To address these issues, this study focused on formulating and characterizing gingerol using nanostructured lipid carriers. Gingerol-loaded NLCs were produced using a two-step process of high-shear homogenization followed by ultrasonication. Different total lipid contents were tested, specifically 5%, 8%, 10%, and 15%. Characterization of the resulting NLCs included particle size, polydispersity index (PDI), zeta potential, entrapment efficiency, in vitro release of gingerol, and stability over 30 days. The findings revealed that the NLC formulation with a total lipid content of 5% yielded the smallest average particle size of 208.32 ± 3.20 nm, alongside the lowest PDI of 0.231 ± 0.014, and the zeta potential measured at -25.90 ± 1.38 mV. The entrapment efficiency for this optimal total lipid was noted to be 70.65 ± 0.75%. Furthermore, stability testing conducted over a designated period demonstrated that the gingerol-loaded NLC formulation with a 5% lipid content maintained its integrity, exhibiting no significant degradation or alteration in properties. The results of this study highlight the critical role of the total lipid content in influencing the characteristics of NLC formulations achieved at 5% total lipid content, which not only improved the properties of gingerol delivery but also presented a potential approach for improving the delivery of compounds with low water solubility such as gingerol.

IntroductionZinc deficiency in children remains a significant health risk, impairing their physical and cognitive maturation. Supplementation with peptide-bound zinc is thought to offer better bioavailability than inorganic zinc salts. Holothuria scabra, commonly referred to as a sea cucumber, contains peptides that may chelate zinc, potentially improving its absorption. The present study aimed to evaluate the efficacy of zinc-chelating peptides from Holothuria scabra (ZCP) supplementation in rat offspring born to zinc-deficient parental rats.MethodsPregnant Sprague Dawley rats were fed either a standard zinc diet (40 mg of zinc per kg of feed) or a zinc-deficient diet (4 mg of zinc per kg of feed). Twelve rat offspring born on the standard zinc diet were randomly assigned to receive either vehicle only or ZCP 40 mg/kg BW. Twenty-four offspring born from zinc-deficient maternal rats were divided into groups that received vehicle only, ZCP 4 mg/kg BW, ZCP 40 mg/kg BW, or ZnSO4 40 mg/kg BW for 3 weeks. At the end of the treatment, serum and intestinal samples were collected and analysed for zinc and metallothionein concentrations, as well as for ZIP2 and ZIP4 mRNA expressions.ResultsZCP supplementation significantly increased serum and duodenal zinc levels, metallothionein concentration, and mRNA expressions of ZIP2/ZIP4 in zinc-deficient rat offspring compared to untreated zinc-deficient ones. Supplementation with ZCP at 4 mg/kg BW showed superior or equivalent improvements compared with ZnSO4 in most parameters.ConclusionZinc chelating peptides from Holothuria scabra improved zinc plasma and duodenal concentrations by enhancing the expression of zinc transporters in zinc-deficient rat offspring. ZCP is a promising alternative to conventional inorganic zinc supplements.

Background Treatment response in acute myeloid leukemia (AML) is influenced by multiple biological and molecular mechanisms. High Mobility Group Box-1 (HMGB-1) is a multifunctional protein involved in inflammation, autophagy, apoptosis, and immunogenic cell death (ICD). Extracellular HMGB-1 released following chemotherapy-induced leukemia cell death may enhance anti-tumor immune responses. This study aimed to evaluate the association between baseline extracellular HMGB-1 protein levels and achievement of complete remission following induction chemotherapy in adult AML patients. Methods A prospective cohort study was conducted at Dharmais National Cancer Center, Jakarta, Indonesia. Adult patients with newly diagnosed AML who received standard D3A7 induction chemotherapy were enrolled consecutively. Baseline extracellular HMGB-1 protein levels were measured using enzyme-linked immunosorbent assay (ELISA) before chemotherapy initiation. Complete remission was assessed by bone marrow examination after induction chemotherapy. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal HMGB-1 cut-off value. Associations between HMGB-1 levels and complete remission were evaluated using relative risks (RRs) with 95% confidence intervals (CIs). Results Seventy-one AML patients were included in the final analysis. The median age at diagnosis was 39 years, and 52.1% were female. Complete remission was achieved in 40 patients (56.3%). Patients with low baseline extracellular HMGB-1 protein levels had a significantly lower probability of achieving complete remission than those with high HMGB-1 levels (RR 0.620; 95% CI 0.394–0.975; p = 0.038), corresponding to an approximately 38% reduction in remission likelihood. Among the evaluated biomolecular markers, extracellular HMGB-1 was the only biomarker significantly associated with complete remission. Conclusion Low baseline extracellular HMGB-1 protein levels are associated with a lower probability of achieving complete remission following induction chemotherapy in adult AML patients. Extracellular HMGB-1 may serve as a potential biomolecular marker of treatment response in AML.

Background: Protein intake is essential for children’s growth. Limited dietary diversity, which is more common in rural areas, can lead to protein deficiency, anemia, and disrupted metabolic processes. The purpose of this study was to explore anemia and amino acid profiles in stunted children living in rural settings. Methods: A total of 80 children, 54 stunted and 26 non-stunted, participated in this study. Collected data included anthropometric measurement (height-for-age Z-score); hematological parameters of red blood cells (RBCs), including the hemoglobin (Hb), hematocrit (Ht), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), erythrocytes; iron status indicators, such as serum iron, total iron binding capacity (TIBC), serum ferritin, transferrin saturation (TS), protein status markers (albumin, total protein), and 21 amino acid profiles. Results: The findings revealed that 63% of stunted children were anemic with low Hb and 24.1% of them was anemic with iron deficiency. Lower levels of albumin and total protein were also observed in stunted children as well as lower concentrations of amino acid arginine and branched-chain amino acids (BCAA), specifically valine and leucine compared to non-stunted children (p<0.05). On the other hand, they exhibited high concentrations of histidine, glycine, tyrosine, asparagine, and citrulline, p<0.05. Conclusions: This study showed that stunted children had anemia and low levels of BCAA.

The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling cascade constitutes an intracellular communication framework that is responsive to cytokines and growth factors, whereas the mitogen-activated protein kinase (MAPK) pathway represents a signaling network activated by extrinsic stimuli such as stress, growth factors, or reactive oxygen species (ROS). This literature review synthesizes scholarly investigations into the roles of the JAK/STAT and MAPK signaling pathways in the progression of chronic obstructive pulmonary disease (COPD), with an emphasis on elucidating the molecular interactions and mechanisms that underlie deficiencies in understanding their contributions to inflammation, immune modulation, and tissue remodeling. The objectives of this review were to assess pathway activation patterns, characterize the molecular structures, and compare the therapeutic strategies. A systematic analysis of multidisciplinary studies employing in vitro, in vivo, clinical, and bioinformatics approaches was conducted. The findings revealed consistent activation of STAT3 and p38 MAPK isoforms by cigarette smoke and inflammatory stimuli, with complex crosstalk shaping macrophage polarization and cytokine production (interleukin-6/IL-6, tumor necrosis factor-α/TNF-α). Therapeutic interventions targeting JAK/STAT and MAPK signaling have the potential to reduce airway inflammation and remodeling, although clinical efficacy remains inconsistent due to corticosteroid resistance and activation of compensatory pathways. Pathway dysregulation correlates with accelerated COPD progression, particularly through epithelial-mesenchymal transition (EMT) and extracellular matrix deposition. Key challenges include balancing pathway modulation to preserve lung homeostasis while avoiding immunosuppressive effects. This analysis highlights the need for precision-targeting strategies to translate molecular insights into effective therapies, thereby providing a framework for future research on COPD pathogenesis and targeted network modulation.

Introduction: It was established that vitamin D reduced insulin resistance in prediabetic rats in a model induced by a high-fat, high-glucose diet and low-dose streptozotocin (HFDS). However, it remained unclear whether vitamin D could assist with obesity and dysbiosis in the insulin-resistant rat model induced by HFDS. Materials and Methods: Twenty-four male Wistar rats in the study were randomly divided into two groups. Six rats were fed a standard diet, while 18 were fed an HFDS diet. Once obesity and insulin resistance were established, the 18 HFDS rats were randomly assigned to three treatment groups for 12 weeks: one group received no treatment, another received 100 IU/kg BW of vitamin D3, and the third received 1000 IU/kg BW of vitamin D3. Body weight and the Lee index were assessed before and after treatment. At the end of the experiment, microbiome profiles of colon segments and epididymal fat adipose tissues were analyzed. Results and Discussion: We found that in a rat model induced by HFDS, vitamin D3 supplementation at both doses reduced body weight, the Lee index, and adipose tissue size, and increased the adiponectin/leptin ratio. The richness and relative abundance of gut microbiome richness and composition alongside improvements in obesity profiles. The main species modulated by vitamin D3 supplementation; notably Lactobacillus spp. and Allobaculum increased, whereas Blautia spp. decreased, particularly at the dose of 1000 IU/kg BW. Conclusions: Vitamin D3 supplementation was associated with improvements in obesity-related parameters, accompanied by changes in the adiponectin/leptin ratio and shifts in gut microbiome diversity and species composition. HIGHLIGHTS Obesity escalates the process of insulin resistance to type 2 diabetes. In our study, vitamin D3 supplementation reduced body weight in an insulin-resistant rat model induced by a high-fat, high-glucose diet and low-dose streptozotocin. The weight loss was accompanied by restored adipokine balance, an increased adiponectin/leptin ratio, decreased adipocyte size, and a shift in microbial composition including increased Lactobacillus and Allobaculum. GRAPHICAL ABSTRACT

Background Phacoemulsification is one of the most frequent surgeries in the world. However, prolonged use of phacoemulsification machines produces reactive oxygen species which will damage corneal endothelial cells. Ascorbic acid has an antioxidant capacity to neutralize oxidative stress in the anterior chamber. This study will investigate the protective effect of ascorbic acid on corneal endothelial cells in patients with hard nuclear cataracts. Methods This study is a double-blinded randomized controlled trial. Samples will be divided into three groups, and 500 mg vitamin C three times daily (1500 mg/day), or placebo will be received for seven weeks. Clinical characteristics, ascorbic acid, malondialdehyde, and total antioxidant capacity of patients in serum and aqueous humor will be measured before and after intervention and phacoemulsification. Conclusions Data from this study will reveal the protective effect of oral vitamin C supplementation on the corneal endothelial cells in patients with hard nucleus cataracts. This trial has been registered at ClinicalTrials.gov (identifier: NCT06781970; registered on 17 January 2025). The trial record is available at: https://clinicaltrials.gov/ct2/show/NCT06781970

Cytochrome P450 isotype 2D6 (CYP2D6) enzyme metabolizes the 8-aminoquinoline primaquine into its active form, 5-hydroxyprimaquine. Highly polymorphic CYP2D6 produces different enzyme activity levels among individuals. This diversity influences the therapeutic efficacy of primaquine in preventing Plasmodium vivax malaria relapses. Urinary 5,6-orthoquinone primaquine concentrations in Indonesian patients treated with primaquine for malaria were analyzed in relation to CYP2D6 genotype-predicted phenotypes and blood methemoglobin levels. We genotyped samples from 48 patients and classified them into three CYP2D6 metabolic activity groups: intermediate, normal, and ultra-rapid metabolizers. Methemoglobin levels were measured repeatedly up to 27 times over 72 h, including one pre-dose measurement and eight post-dose measurements per day at approximately 30-min intervals following primaquine administration. Intermediate metabolizers exhibited significantly lower urinary concentrations of 5,6-orthoquinone primaquine compared to normal and ultra-rapid metabolizers (geometric mean ratio: 2.24, 95% CI: 1.26-3.98, P = 0.01), indicative of reduced drug bioactivation. Methemoglobin concentrations gradually increased from Day 0 to Day 2, particularly in normal metabolizers. Day 2 methemoglobin levels were higher in normal/ultra-rapid metabolizers in our study sample (geometric mean ratio = 1.51; 95% CI: 0.84-2.70; P = 0.15). There was a strong positive relationship between urinary 5,6-orthoquinone primaquine and Day 2 methemoglobin levels (geometric mean ratio per 1,000 ng/mL increase = 1.90; 95% CI: 1.37-2.63; P = 0.0007). Our findings accord with the hypothesized utility of urinary 5,6-orthoquinone primaquine concentrations and methemoglobin levels as pharmacodynamic markers of primaquine bioactivation. Understanding and measuring the impacts of CYP2D6 polymorphisms will aid in interpreting clinical trials and optimizing primaquine dosing strategies.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT03916003.

Background and Objectives:Cardiac hypertrophy is a maladaptive response to chronic hypertension and is often associated with impaired calcium handling. Andrographolide, a bioactive diterpenoid, has shown cardioprotective effects in several preclinical models, but its role in pressure-overload-induced hypertrophy remains unclear. This study evaluated the effects of andrographolide on cardiac hypertrophy, calcium-handling gene expression, and plasma B-type natriuretic peptide (BNP) levels in a deoxycorticosterone acetate (DOCA)-salt rat model of hypertension. Materials and Methods:Fifteen male Sprague-Dawley rats underwent unilateral nephrectomy followed one week later by DOCA administration (20 mg/kg, subcutaneous, twice weekly) and 1% NaCl drinking water. After two weeks of DOCA-salt exposure, rats were randomized to receive oral andrographolide (30 mg/kg/day in 0.5% carboxymethyl cellulose) or no treatment. Blood pressure was measured at weeks 2 and 5 using a tail-cuff system. At week 5, echocardiography was performed, followed by euthanasia and collection of cardiac tissue and plasma. BNP and cardiac calcium levels were measured by enzyme-linked immunosorbent assay and colorimetric assay, respectively. Sarco/endoplasmic reticulum Ca2+-ATPase 2a (SERCA2a) and ryanodine receptor (RyR) mRNA expression were quantified by PCR using β-actin as the reference gene. Results:DOCA-salt treatment significantly increased blood pressure, left ventricular hypertrophy indices, plasma BNP, and cardiac calcium levels. Andrographolide attenuated these changes and restored SERCA2a and RyR expression. Conclusion:Andrographolide alleviates DOCA-salt-induced cardiac hypertrophy, likely by restoring calcium-handling pathways, supporting its therapeutic potential in hypertension-induced cardiac remodeling.

OBJECTIVE:TMEPAI (transmembrane prostate androgen-induced protein) is one of the proteins associated with the resistance of triple-negative breast cancer (TNBC) to various cytotoxic medicines. However, it has remained uncertain how TMEPAI mechanistically contributes to TNBC resistance to paclitaxel. Thus, this study aimed to investigate the effect and possible mechanism of TMEPAI gene editing via CRISPR-Cas9 on the response of triple-negative breast cancer cells to paclitaxel. METHODS:The present study was conducted on wild-type triple-negative breast cancer cells (BT-549) and BT-549 cells with TMEPAI knocked out using CRISPR-Cas9. Both cell types underwent treatment with TGF-β, followed by paclitaxel, and were evaluated for cell viability and the expression of cell proliferation, apoptosis, drug efflux transporters, and epithelial-mesenchymal transition markers. RESULT:TMEPAI knock-out cells exhibited a markedly increased susceptibility to paclitaxel, as characterized by decreased viability and elevated expression of pro-apoptotic genes (Bax, caspase-3, caspase-9), as well as a reduction in anti-apoptotic markers (Bcl-2). The presence of TMEPAI perpetuated the phosphorylation of AKT (pAKT/AKT), elevated the expression of drug efflux transporters (particularly P-glycoprotein and MRP-1), and facilitated epithelial-mesenchymal transition (EMT), as evidenced by increased levels of Snail, Zeb1, and Twist. All these effects were diminished in TMEPAI-knock-out triple-negative breast cancer cells. CONCLUSION:TMEPAI appears to facilitate paclitaxel resistance in triple-negative breast cancer cells by promoting cell survival signaling, inhibiting apoptosis, enhancing drug efflux, and initiating epithelial-mesenchymal transition (EMT). Targeting TMEPAI may be a viable approach to overcoming resistance and improving treatment outcomes in triple-negative breast cancer cells.

Plant-derived exosome-like nanoparticles (PDELNs) represent a promising frontier in nanomedicine, offering natural alternatives to synthetic drug delivery systems. These membrane-bound vesicles, typically 30-150 nm in size, contain bioactive compounds and demonstrate potential for cross-kingdom communication with mammalian cells. This objective study is to evaluate PEG-based and ultracentrifugation methods, benchmark hybrid approaches, compare emerging alternatives, and assess their impact on biomedical applications. A systematic analysis of diverse studies employing comparative yield, purity, bioactivity, scalability, and complexity metrics was conducted. A systematic search of 3 databases SciSpace Deep Search; Google Scholar; MEDLINE (2016-2024) following PRISMA guidelines, 52 studies met the inclusion criteria with combined terms : ``plant exosome'' AND (``PEG precipitation'' OR ``polyethylene glycol'' OR ``ultracentrifugation'' OR ``hybrid methods'') AND ``biomedical applications''. Findings indicate that PEG-based precipitation offers higher or comparable yields with greater scalability and cost-effectiveness but lower purity due to protein co-precipitation; ultracentrifugation yields purer exosomes with preserved bioactivity yet is resource-intensive and less scalable; hybrid methods combining PEG precipitation with ultracentrifugation or size-exclusion chromatography balance yield and purity while increasing procedural complexity. Emerging techniques, such as immunoaffinity capture, enhance specificity but face limitations in plant systems. Overall, optimized hybrid protocols improve isolation quality and bioactivity retention, supporting translational potential. These insights underscore the need for standardized, scalable isolation strategies tailored to plant exosomes to advance their clinical and biomedical applications.

Atorvastatin calcium is an antihyperlipidemic with low bioavailability, and to address this limitation, a transdermal delivery system utilizing transethosomes as a carrier was developed. This study aimed to enhance the bioavailability of atorvastatin calcium by transitioning from oral to transdermal administration. The six different formulas of transethosomes were observed based on particle size, PDI, zeta potential, deformability index, and morphology. Furthermore, the patch's characteristics, penetration, pharmacokinetic, and irritation studies of transethosomes patch were observed. The results showed that atorvastatin calcium transethosomes had a particle size of ≤ 130.59 nm with PDI and zeta potential values of ≤ 0.24 and ≥ -51.87 mV, respectively. The vesicles featured spherical morphology and an excellent deformability index. The transethosome patches obtained had a pH and viscosity value of 5.7 and ≥ 8741 mPa.s, respectively. The properties of transethosomes loaded in the patch were observed to show a particle size of ≤ 249.83 nm and zeta potential ≥ -44.73 mV. A penetration study of the atorvastatin calcium transethosomes patch reveals high flux, especially the G6 formula, increasing bioavailability by 3.67-fold and not irritating. In conclusion, developing a transethosomes patch for transdermal delivery proved to be an effective method for enhancing the bioavailability of atorvastatin calcium.

Background: Chemotherapeutics like 5-fluorouracil (5-FU) may induce a variety of adverse effects, including oral mucositis (OM), which may necessitate treatment discontinuation in patients with cancer. Currently, only a few models of OM are available for studying many aspects of pathophysiology and treatments. Aim: The current study examined the clinical and histological aspects of 5-fluorouracil-induced oral mucositis (5FU-OM) in rats. Methods: We randomly divided 19 male Sprague-Dawley rats into 8 healthy rats and 11 that received a single dose of 5FU-OM. On the first day of the experiment, the 5FU-OM group was administered an intraperitoneal injection of 5-FU (150-mg/kg BW), whereas the healthy group was not administered the drug. The third day involved scratching the oral mucosa of all rats in both groups. Clinical observations included changes in body weight, food consumption, hair loss, and severity of oral lesions. At the end of the study, we collected cardiac blood and mucosal tissue samples to investigate hematological and histological alterations. Results: Our findings demonstrated that a single intraperitoneal injection of 5-FU and mucosal irritation might result in ulcerative OM. We discovered other clinical toxicities caused by chemotherapy, such as weight loss, red lacrimation, facial edema, epistaxis, and hair loss. 5-FU also produced hematological abnormalities, including anemia and thrombocytopenia. Histopathological changes included ulceration, bleeding, vasodilation, edema, and inflammatory cell infiltration. Conclusion: This simple rat model of OM accurately replicates the clinical and histological mucosal responses to chemotherapy, including its systemic adverse effects. Thus, it can be used in research on OM.

N-acetylcysteine (NAC) is known to enhance neuroplasticity and help reduce smoking addiction by modulating brain metabolites. The use of magnetic resonance spectroscopy (MRS) in smokers receiving NAC as an adjuvant to motivational enhancement therapy (MET) represents a novel approach to understanding how this combination therapy influences brain chemistry. By utilizing MRS, the effectiveness of NAC can be quantitatively assessed by analyzing changes in smoking-affected brain metabolites. The aim of this study was to evaluate the efficacy of NAC combined with MET for nicotine addiction, using MRS to assess neurochemical alterations associated with treatment response. A stratified, randomized, parallel-group clinical trial was conducted, comparing NAC and MET combination to MET only among smokers. The study analyzed the effectiveness of NAC by evaluating glutamate-glutamine (Glx) to creatine ratio (Glx/creatine ratio) and N-acetylaspartate (NAA) to creatine ratio (NAA/creatine ratio) in the nucleus accumbens, bilateral cerebellum, medial prefrontal cortex, ventromedial prefrontal cortex, and bilateral precuneus. Our data indicated that the Glx/creatine ratios for the intervention versus control groups were as follows: nucleus accumbens (0.68 vs 0.43), bilateral cerebellum (0.68 vs 0.43), left medial prefrontal cortex (1.11 vs 0.82), ventromedial prefrontal cortex (0.32 vs 0.86), and bilateral precuneus (0.75 vs 0.58). The NAA/creatine ratios for the intervention versus control groups were as follows: nucleus accumbens (3.55 vs 8.35), bilateral cerebellum (7.82 vs 4.02), left medial prefrontal cortex (5.47 vs 5.20), ventromedial prefrontal cortex (3.55 vs 7.46), and bilateral precuneus (4.73 vs 4.00). Our analysis indicated that the Glx/creatine ratio was higher in the intervention group than in the control group in the medial prefrontal cortex (p=0.02), while the NAA/creatine ratio was higher in the intervention group than in the control group in the bilateral cerebellum (p<0.001). The reported side effects were mild to moderate discomfort and well-tolerated across both groups. These findings highlight the potential of NAC and MET combination in promoting neuroplasticity and supporting nicotine addiction treatment.

Background and objectives: Pregnant mothers with obesity may increase the risk of adverse health outcomes for their infants, such as weakened immune systems. Currently, there is no standardized treatment for obese pregnant women to reduce risks to the mothers and their infants. Zingiber officinale (ginger) is a commonly used medicinal plant to relieve symptoms associated with hyperemesis gravidarum. The bioactive compounds in ginger are recognized for their anti-obesity and anti-inflammatory properties. Our objective was to investigate how the phytochemical components of ginger may interact with immune response proteins related to infants of obese mothers, employing a network pharmacology approach. Method: The target proteins were obtained from Gene Cards, and the chemical structures were sourced from PubChem. Protein-protein interactions were constructed using Cytoscape. Interactions between phytochemicals from ginger and target genes were illustrated, followed by enrichment analysis and molecular docking. Results: Through network pharmacology and molecular docking, we identified 36 bioactive compounds in Zingiber officinale that modulate key proteins (TLR4, NF-kappa B, TNF-alpha) involved in inflammation and cytokine production. The main phytoconstituents, 6-gingerol, and 6-shogaol, demonstrated strong binding affinity to TLR4, as revealed by the docking analysis, identifying them as ligands that bind effectively to the target protein TLR4. This finding is significant, given TLR4's role in addressing obesity-related developmental inflammation. Conclusion: This study emphasizes the immunomodulatory potential of bioactive compounds from Zingiber officinale, particularly 6-gingerol and 6-shogaol, in addressing immune system dysregulation associated with obesity in children born to obese mothers, focusing on key targets such as TLR4, NF-kappa B, and TNF-alpha.