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Microglia M1 phenotype causes HPA axis hyperactivity, neurotransmitter dysfunction, and production of proinflammatory mediators and oxidants, which may contribute to the etiology of depression and neurodegenerative diseases. Eicosapentaenoic acid (EPA) may counteract neuroinflammation by increasing n-3 docosapentaenoic acid (DPA). However, the cellular and molecular mechanisms of DPA, as well as whether it can exert antineuroinflammatory and neuroprotective effects, are unknown. The present study first evaluated DPA’s antineuroinflammatory effects in lipopolysaccharide (LPS)-activated BV2 microglia. The results showed that 50 μM DPA significantly decreased BV2 cell viability after 100 ng/mL LPS stimulation, which was associated with significant downregulation of microglia M1 phenotype markers and proinflammatory cytokines but upregulation of M2 markers and anti-inflammatory cytokine. Then, DPA inhibited the activation of mitogen-activated protein kinase (MAPK) p38 and nuclear factor-κB (NF-κB) p65 pathways, which results were similar to the effects of NF-κB inhibitor, a positive control. Second, BV2 cell supernatant was cultured with differentiated SH-SY5Y neurons. The results showed that the supernatant from LPS-activated BV2 cells significantly decreased SH-SY5Y cell viability and brain-derived neurotrophic factor (BDNF), TrkB, p-AKT, and PI3K expression, which were significantly reversed by DPA pretreatment. Furthermore, DPA neuroprotection was abrogated by BDNF-SiRNA. Therefore, n-3 DPA may protect neurons from neuroinflammation-induced damage by balancing microglia M1 and M2 polarizations, inhibiting microglia-NF-κB and MAPK p38 while activating neuron-BDNF/TrkB-PI3K/AKT pathways.

Clinical evidence indicated that eicosapentaenoic acid (EPA) was more effective than docosahexaenoic acid (DHA) in depression treatment. However, possible mechanisms remain unclear. Here, a chronic unpredictable mild stress (CUMS)-induced model of depression was used to compare EPA and DHA anti-depressant effects. After EPA or DHA feeding, depression-like behavior, brain n-3/n-6 PUFAs profile, serum corticosterone and cholesterol concentration, hippocampal neurotransmitters, microglial and astrocyte related function, as well as neuronal apoptosis and survival signaling pathways were studied. EPA was more effective than DHA to ameliorate CUMS-induced body weight loss, and depression-like behaviors, such as increasing sucrose preference, shortening immobility time and increasing locomotor activity. CUMS-induced corticosterone elevation was reversed by bother fatty acids, while increased cholesterol was only reduced by EPA supplement. Lower hippocampal noradrenaline and 5-hydroxytryptamine concentrations in CUMS rats were also reversed by both EPA and DHA supplement. However, even though CUMS-induced microglial activation and associated increased IL-1β were inhibited by both EPA and DHA supplement, increased IL-6 and TNF-α levels were only reduced by EPA. Compared to DHA, EPA could improve CUMS-induced suppressive astrocyte biomarkers and associated BDNF-TrkB signaling. Moreover, EPA was more effective than DHA to attenuate CUMS-induced higher hippocampal NGF, GDNF, NF-κB, p38, p75, and bax expressions, but reversed bcl-2 reduction. This study for the first time revealed the mechanisms by which EPA was more powerful than DHA in anti-inflammation, normalizing astrocyte and neurotrophin function and regulating NF-κB, p38 and apoptosis signaling. These findings reveal the different mechanisms of EPA and DHA in clinical depression treatment.

Sarcopenia is a syndrome characterized by progressive loss of skeletal muscle mass, strength and function, which is one of the most important clinical features of cancer malnutrition, representing a poor prognostic indicator in oncology. Sarcopenia is commonly assessed by measuring the skeletal muscle index (SMI) of the third lumbar spine (L3) using computed tomography (CT). The primary aim of this meta‐analysis was to study the association between low SMI and comprehensive clinicopathological characteristics as well as prognosis in patients with ovarian cancer. Data were searched in PubMed, EMBASE and Cochrane databases from inception to 10 June 2022. Studies evaluating the prognostic effect of SMI on ovarian cancer survival or chemotherapy‐related side effects were included. The risk of bias and study quality were assessed via the Newcastle–Ottawa Scale (NOS). The search strategy yielded 1286 hits in all three databases combined. Thirteen studies were included for qualitative and quantitative analysis, comprising 1814 patients. Our meta‐analysis revealed the significant association between low SMI and progression‐free survival (PFS) [P = 0.02; hazard ratio (HR): 1.40, 95% confidence interval (CI): 1.06–1.85], as well as 5‐year overall survival (OS) [P = 0.02; odds ratio (OR): 1.35, 95% CI: 1.05–1.74]. Low SMI was also obviously associated with body mass index (BMI) < 25 (P < 0.00001; OR: 5.08, 95% CI: 3.54–7.30), FIGO stage (P = 0.02; OR: 1.62, 95% CI: 1.06–2.45) and R0 cytoreduction (P = 0.04;OR: 1.34, 95% CI: 1.01–1.79). There was no correlation between low SMI and histological types, pathological grades and chemotherapy‐related toxicity. The quality of the evidence was relatively high according to NOS. Our meta‐analysis indicated that sarcopenia assessed by SMI was associated with poor clinical characteristics and adverse prognosis in patients with ovarian cancer. Consensus should be reached on standardized cut‐off values for defining sarcopenia in patients with ovarian cancer.

Euryale ferox Salisb. (prickly water lily) is the only extent of the genus Euryale that has been widely distributed in China, India, Korea, and Japan. The seeds of E. ferox (EFS) have been categorized as superior food for 2000 years in China, based on their abundant nutrients including polysaccharides, polyphenols, sesquineolignans, tocopherols, cyclic dipeptides, glucosylsterols, cerebrosides, and triterpenoids. These constituents exert multiple pharmacological effects, such as antioxidant, hypoglycemic, cardioprotective, antibacterial, anticancer, antidepression, and hepatoprotective properties. There are very few summarized reports on E. ferox, albeit with its high nutritional value and beneficial activities. Therefore, we collected the reported literature (since 1980), medical classics, database, and pharmacopeia of E. ferox, and summarized the botanical classification, traditional uses, phytochemicals, and pharmacological effects of E. ferox, which will provide new insights for further research and development of EFS-derived functional products.

Neuroinflammatory microenvironment, regulating neurite regrowth and neuronal survival, plays a critical role in Alzheimer’s disease (AD). During neuroinflammation, microglia are activated, inducing the release of inflammatory or anti-inflammatory factors depending on their polarization into classical M1 microglia or alternative M2 phenotype. Therefore, optimizing brain microenvironment by small molecule-targeted microglia polarization and promoting neurite regeneration might be a potential therapeutic strategy for AD. In this study, we found platycodigenin, a naturally occurring triterpenoid, promoted M2 polarization and inhibited M1 polarization in lipopolysaccharide (LPS)-stimulated BV2 and primary microglia. Platycodigenin downregulated pro-inflammatory molecules such as interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-6 and nitric oxide (NO), while upregulated anti-inflammatory cytokine IL-10. Further investigation confirmed that platycodigenin inhibited cyclooxygenase-2 (Cox2) positive M1 but increased Ym1/2 positive M2 microglial polarization in primary microglia. In addition, platycodigenin significantly decreased LPS-induced the hyperphosphorylation of mitogen-activated protein kinase (MAPK) p38 and nuclear factor-κB (NF-κB) p65 subunits. Furthermore, the inactivation of peroxisome proliferators-activated receptor γ (PPARγ) induced by LPS was completely ameliorated by platycodigenin. Platycodigenin also promoted neurite regeneration and neuronal survival after Aβ treatment in primary cortical neurons. Taken together, our study for the first time clarified that platycodigenin effectively ameliorated LPS-induced inflammation and Aβ-induced neurite atrophy and neuronal death.

Natural medicines are attractive sources of leading compounds that can be used as interventions for neurodegenerative disorders. The complexity of their chemical components and undetermined bio-metabolism have greatly hindered both the use of natural medicines and the identification of their active constituents. Here, we report a systematic strategy for evaluating the bioactive candidates in natural medicines used for Alzheimer's disease (AD). We found that Drynaria Rhizome could enhance memory function and ameliorate AD pathologies in 5XFAD mice. Biochemical analysis led to the identification of the bio-effective metabolites that are transferred to the brain, namely, naringenin and its glucuronides. To explore the mechanism of action, we combined the drug affinity responsive target stability with immunoprecipitation-liquid chromatography/mass spectrometry analysis, identifying the collapsin response mediator protein 2 protein as a target of naringenin. Our study indicates that biochemical analysis coupled with pharmacological methods can be used in the search for new targets for AD intervention.

Background Federally Qualified Health Centers (FQHCs) are a critical source of care for medically underserved populations and often serve as medical homes for individuals with serious mental illness (SMI). Many FQHCs provide mental health services and could facilitate access to mental health treatment within and outside of FQHCs. This study compared mental health care utilization and acute care events for adult Medicaid enrollees with SMI who receive care at Federally Qualified Health Centers (FQHCs) vs. other settings. Methods This study used the 2015–2016 Massachusetts All-Payer Claims Database to examine outpatient mental health care and acute care events for 32,330 Medicaid adults, ages 18–64 and with major depressive, bipolar, or schizophrenia spectrum disorders (SSD), who resided in FQHC service areas and received care from FQHCs vs. other settings in 2015. Multivariable linear regressions assessed associations between receiving care at FQHCs and outpatient mental health visits, psychotropic medication fills, and acute care events in 2016. Results There were 8,887 (27.5%) adults in the study population ( N  = 32,330) who had at least one FQHC visit in 2015. Those who received care at FQHCs were more likely to have outpatient mental health visits (73.3% vs. 71.2%) and psychotropic medication fills (73.2% vs. 69.0%, both p  < .05), including antidepressants among those with depressive disorders and antipsychotics among those with SSD. They were more likely to have ED visits (74.0% vs. 68.7%), but less likely to be hospitalized (27.8% vs. 31.9%, both p  < .05). However, there was no significant difference in the likelihood of having an acute psychiatric hospitalization (9.5% vs. 9.8%, p  = .35). Conclusions Among Medicaid enrollees with SMIs who had access to care at FQHCs, those receiving care at FQHCs were more likely to have outpatient mental health visits and psychotropic medication fills, with lower rates of hospitalization, suggesting potentially improved quality of outpatient care. Higher ED visit rates among those receiving care at FQHCs warrant additional investigation.

Neuroinflammation induced by microglial and astrocyte polarizations may contribute to neurodegeneration and cognitive impairment. Omega (n)-3 polyunsaturated fatty acids (PUFAs) have anti-inflammatory and neuroprotective effects, but conflicting results were reported after different n-3 PUFA treatments. This study examined both the change in glial polarizations in ageing rats and the differential effects of two omega-3 PUFAs. The results showed that both PUFAs improved spatial memory in ageing rats, with docosahexaenoic acid (DHA) being more effective than eicosapentaenoic acid (EPA). The imbalance between microglial M1/M2 polarizations, such as up-regulating ionized calcium binding adaptor molecule 1 (IBA1) and down-regulating CD206 and arginase-1 (ARG-1) was reversed in the hippocampus by both n-3 PUFAs, while the DHA effect on CD206 was stronger. Astrocyte A1 polarization presented increasing S100B and C3 but decreasing A2 parameter S100A10 in the ageing brain, which were restored by both PUFAs, while DHA was more effective on S100A10 than EPA. Consistent with microglial M1 activation, the concentration of pro-inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 were significantly increased, which were attenuated by DHA, while EPA only suppressed IL-6. In correlation with astrocyte changes, brain-derived neurotrophic factor precursor was increased in ageing rats, which was more powerfully down-regulated by DHA than EPA. In summary, enhanced microglial M1 and astrocytic A1 polarizations may contribute to increased brain pro-inflammatory cytokines, while DHA was more powerful than EPA to alleviate ageing-associated neuroimmunological changes, thereby better-improving memory impairment.

Neuroinflammation is one of the main mechanisms involved in the progression of neurodegenerative diseases (NDs), and microglial activation is the main feature of neuroinflammation. Polaprezinc (Pol), a chelator of L-carnosine and zinc, is widely used as a clinical drug for gastric ulcers. However, its potential effects on NDs remain unexplored. In LPS-induced BV-2 microglia, we found that Pol reduced the generation of NO and ROS and revealed inhibited expression of iNOS, COX-2, and inflammatory factors such as IL-6, TNF-α, and 1L-1β by Pol using qRT-PCR and Western blotting. These effects were found to be associated with the suppression of the NF-κB signaling pathway. Moreover, we evaluated the potential synergistic effects of aspergillusidone G (Asp G) when combined with Pol. Remarkably, co-treatment with low doses of Asp G enhanced the NO inhibition by Pol from approximately 30% to 80% in LPS-induced BV2 microglia, indicating a synergistic anti-inflammatory effect. A bioinformatics analysis suggested that the synergistic mechanism of Asp G and Pol might be attributed to several targets, including NFκB1, NRF2, ABL1, TLR4, and PPARα. These findings highlight the anti-neuroinflammatory properties of Pol and its enhanced efficacy when combined with Asp G, proposing a novel therapeutic strategy for managing neuroinflammation in NDs.

Ovarian cancer is the most lethal gynecological malignancy with high recurrence rates and low survival rates, remaining a disease of high unmet need. Cancer immunotherapy, which harnesses the potential of the immune system to attack tumors, has emerged as one of the most promising treatment options in recent years. As an important form of immunotherapy, dendritic cell (DC)–based vaccines have demonstrated the ability to induce an immune response, while clinical efficacy of DC vaccines remains unsubstantiated as long‐term benefit is only reported in a restricted proportion of patients. Here, a biomimetic nanovaccine derived from DCs is developed through cell membrane coating nanotechnology. This nanovaccine, denoted “mini DC,” inherits the ability of antigen presentation and T cells' stimulation from DCs and is shown to elicit enhanced activation of T cells both in vitro and in vivo. In a mouse model of ovarian cancer, mini DCs exhibit superior therapeutic and prophylactic efficacy against cancer including delayed tumor growth and reduced tumor metastasis compared with DC vaccine. These findings suggest that mini DCs may serve as a facile and potent vaccine to boost anticancer immunotherapy. This work reports a biomimetic nanovaccine derived from dendritic cells (DCs). This nanovaccine possesses abilities of antigen presentation and T cells' stimulation and is shown to elicit enhanced activation of T cells both in vitro and in vivo. It also exhibits superior therapeutic and prophylactic efficacy against tumors compared with DC vaccine in a mouse model of ovarian cancer.