Obesity-induced insulin resistance and type 2 diabetes mellitus (T2DM) represent complex systemic disorders marked by chronic inflammation, oxidative stress, mitochondrial dysfunction, and endoplasmic reticulum (ER) stress. These pathophysiological processes disrupt insulin signaling and β-cell function, leading to impaired glucose homeostasis across multiple organs. Conventional therapies often target isolated pathways, overlooking the intricate molecular crosstalk and organelle-level disturbances driving disease progression. Citrus-derived polyphenols—including hesperidin, naringenin, nobiletin, and tangeretin—have emerged as promising agents capable of orchestrating a multi-targeted “metabolic reprogramming.” These compounds modulate key signaling pathways, including AMPK, PI3K/Akt, NF-κB, and Nrf2, thereby enhancing insulin sensitivity, reducing pro-inflammatory cytokine expression, and restoring redox balance. Furthermore, they improve mitochondrial biogenesis, stabilize membrane potential, and alleviate ER stress by modulating the unfolded protein response (UPR), thus supporting cellular energy homeostasis and protein folding capacity. Evidence from preclinical studies and select clinical trials suggests that citrus polyphenols can significantly improve glycemic control, reduce oxidative and inflammatory markers, and preserve β-cell function. Their pleiotropic actions across molecular and organ-level targets position them as integrative metabolic modulators. This review presents a systems-level synthesis of how citrus polyphenols rewire metabolic signaling networks and organelle resilience, offering a holistic therapeutic strategy to mitigate the root causes of obesity-induced insulin resistance.

Drug addiction is a rising concern globally that has deeply attracted the attention of the healthcare sector. The United States is not an exception, and the drug addiction crisis there is even more serious, with 10% of adults having faced substance use disorder, while around 75% of this number has been reported as not having received any treatment. Surprisingly, there are annually over 70,000 deaths reported as being due to drug overdose. Researchers are continually searching for solutions, as the current strategies have been ineffective. Health informatics platforms like electronic health records, telemedicine, and the clinical decision support system have great potential in tracking the healthcare data of patients on an individual basis and provide precise medical support in a private space. Such technologies have been found to be useful in identifying the risk factors of drug addiction among people and mitigating them. Moreover, the platforms can be used to check prescriptions of addictive drugs such as opioids and caution healthcare providers. Programs such as the Prescription Drug Monitoring Program (PDMP) and the Drug and Alcohol Services Information Systems (DASIS) are already in action in the US, but the situation demands more in-depth studies in order to mitigate substance use disorders. Artificial intelligence (AI), when combined with health informatics, can aid in the analysis of large amounts of patient data and aid in classifying nature of addiction to assist in the provision of personalized care.

Background: Diabetes and mental health conditions frequently co-occur, with depression and anxiety affecting up to 20–30% of people with diabetes. These comorbidities worsen glycemic control, adherence, and quality of life, yet mental health is often neglected in diabetes care. Integrating mental health services into diabetes management is recommended by international organizations to improve patient outcomes. Objectives: To systematically review the evidence on integrated mental health interventions in diabetes care, compared to usual diabetes care, in improving patient outcomes (glycemic control, mental health, adherence, quality of life). Methods: We searched PubMed/MEDLINE, Embase, PsycINFO, and Scopus (2000 through July 2024) for studies of diabetes care integrating mental health support (e.g., collaborative care, co-location, stepped care, or digital interventions). Inclusion criteria were controlled trials or cohort studies involving individuals with type 1 or type 2 diabetes receiving an integrated mental health intervention, with outcomes on glycemic control and/or mental health. Two reviewers independently screened titles/abstracts and full texts, with disagreements resolved by consensus. Data on study design, population, intervention components, and outcomes were extracted. Risk of bias was assessed using Cochrane or appropriate tools. Results: Out of records identified, 64 studies met inclusion criteria (primarily randomized controlled trials). Integrated care models consistently improved depression and anxiety outcomes and diabetes-specific distress, and yielded modest but significant reductions in glycated hemoglobin (HbA1c) compared to usual care. Many interventions also enhanced treatment adherence and self-management behaviors. For example, collaborative care trials showed greater depression remission rates and small HbA1c improvements (~0.3–0.5% absolute reduction) relative to standard care. Co-located care in diabetes clinics was associated with reduced diabetes distress, depression scores, and HbA1c over 12 months. Digital health integrations (telepsychiatry, online cognitive-behavioral therapy) improved psychological outcomes and adherence, with some reporting slight improvements in glycemic control. Integrated approaches often increased uptake of mental health services (e.g., higher referral completion rates) and showed high patient satisfaction. A subset of studies reported fewer emergency visits and hospitalizations with integrated care, and one economic analysis found collaborative care cost-effective in primary care settings. Conclusions: Integrating mental health into diabetes care leads to better mental health outcomes and modest improvements in glycemic control, without adverse effects. Heterogeneity across studies is noted, but the overall evidence supports multidisciplinary, patient-centered care models to address the psychosocial needs of people with diabetes. Healthcare systems should prioritize implementing and scaling integrated care, accompanied by provider training and policy support, to improve outcomes and bridge the persistent treatment gap. Future research should focus on long-term effectiveness, cost-effectiveness, and strategies to reach diverse populations.

Background: Schizophrenia is a complex neuropsychiatric disorder whose pathophysiology may involve oxidative stress-induced neuronal damage and inflammation. We conducted a cross-species study to elucidate oxidative stress dysregulation in schizophrenia. Methods: We measured peripheral oxidative stress biomarkers (malondialdehyde [MDA], nitric oxide [NO], reduced glutathione [GSH], superoxide dismutase [SOD], catalase [CAT], advanced protein oxidation products [APOP]), and C-reactive protein (CRP) in antipsychotic-naïve schizophrenia patients and matched controls. We also assayed liver enzymes (ALP, ALT, AST) as indicators of systemic metabolic stress. In parallel, we re-analyzed published single-cell RNA-sequencing data from a Setd1a^+/–^ mouse model of schizophrenia, focusing on prefrontal cortex (PFC) cell types and oxidative stress-related gene expression. Results: Patients with schizophrenia showed markedly elevated MDA and NO (indicators of lipid and nitrosative stress) and significantly reduced antioxidant defenses (GSH, SOD, CAT) versus controls (p < 0.01 for all comparisons). Notably, urban patients exhibited higher oxidative stress biomarker levels than rural patients, implicating environmental contributions. Liver function tests revealed increased ALT, AST, and ALP in schizophrenia, suggesting hepatic/metabolic dysregulation. Single-cell analysis confirmed dysregulated redox pathways in the schizophrenia model; PFC neurons from Setd1a^+/–^ mice displayed significantly lower expression of key antioxidant genes (e.g., Gpx4, Nfe2l2) compared to wild-type, indicating impaired glutathione metabolism. Conclusions: Our integrative data identify convergent oxidative stress imbalances in schizophrenia across species. These findings advance a mechanistic understanding of schizophrenia as a disorder of redox dysregulation and inflammation. They also have translational implications as augmenting antioxidant defenses (for example, with N-acetylcysteine or vitamins C/E) could mitigate oxidative injury and neuroinflammation in schizophrenia, representing a promising adjunct to antipsychotic therapy.

Drug addiction is a complex issue influenced by biological, psychological, and social factors. Historically, substance use disorders (SUDs) have been studied primarily in men, overlooking crucial gender differences. However, emerging research reveals that women exhibit unique drug use patterns, distinct neurobiological responses, and specific psychosocial challenges in addiction and recovery. Understanding these differences is essential for developing gender-sensitive prevention and treatment approaches. Neurobiologically, sex hormones such as estrogen and progesterone modulate drug sensitivity, leading to a faster progression from initial use to dependence in women. The mesolimbic dopamine system and prefrontal cortex demonstrate sex-specific activity, influencing cravings, reward processing, and relapse vulnerability. Additionally, hormonal fluctuations and stress responses contribute to more severe withdrawal symptoms and increased relapse risk in women. Social and psychological factors further differentiate addiction in women. They are more likely to use substances as a coping mechanism for trauma, anxiety, and depression. Gender roles and societal stigma discourage help-seeking, while caregiving responsibilities, economic dependence, and intimate partner relationships create additional treatment barriers. Women also face heightened risks of substance-related violence and exploitation Despite these challenges, gender-responsive interventions incorporating trauma-informed care, mental health support, and social empowerment strategies have shown promising outcomes. Addressing co-occurring psychiatric disorders and providing childcare support can enhance rehabilitation success. However, addiction research remains predominantly male-focused, necessitating a paradigm shift toward inclusive, gender-sensitive treatment frameworks. This review synthesizes neurobiological, social, and psychological perspectives to guide more effective, tailored interventions for women.

Obesity-induced insulin resistance and type 2 diabetes mellitus (T2DM) represent complex systemic disorders marked by chronic inflammation, oxidative stress, mito-chondrial dysfunction, and endoplasmic reticulum (ER) stress. These pathophysiologi-cal processes disrupt insulin signaling and β-cell function, leading to impaired glucose homeostasis across multiple organs. Conventional therapies often target isolated pathways, overlooking the intricate molecular crosstalk and organelle-level disturb-ances driving disease progression. Citrus-derived polyphenols—including hesperidin, naringenin, nobiletin, and tange-retin have emerged as promising agents capable of orchestrating a multi-targeted “metabolic reprogramming.” These compounds modulate key signaling pathways, in-cluding AMPK, PI3K/Akt, NF-κB, and Nrf2, thereby enhancing insulin sensitivity, re-ducing pro-inflammatory cytokine expression, and restoring redox balance. Further-more, they improve mitochondrial biogenesis, stabilize membrane potential, and alle-viate ER stress by modulating the unfolded protein response (UPR), thus supporting cellular energy homeostasis and protein folding capacity. Evidence from preclinical studies and select clinical trials suggests that citrus poly-phenols can significantly improve glycemic control, reduce oxidative and inflamma-tory markers, and preserve β-cell function. Their pleiotropic actions across molecular and organ-level targets position them as integrative metabolic modulators. This review presents a systems-level synthesis of how citrus polyphenols rewire metabolic signal-ing networks and organelle resilience, offering a holistic therapeutic strategy to miti-gate the root causes of obesity-induced insulin resistance.