Bruch's-Mimetic Nanofibrous Membranes Functionalized with the Integrin-Binding Peptides as a Promising Approach for Human Retinal Pigment Epithelium Cell Transplantation.

BACKGROUND: This study aimed to develop an ultrathin nanofibrous membrane able to, firstly, mimic the natural fibrous architecture of human Bruch's membrane (BM) and, secondly, promote survival of retinal pigment epithelial (RPE) cells after surface functionalization of fibrous membranes. METHODS: Integrin-binding peptides (IBPs) that specifically interact with appropriate adhesion receptors on RPEs were immobilized on Bruch's-mimetic membranes to promote coverage of RPEs. Surface morphologies, Fourier-transform infrared spectroscopy spectra, contact angle analysis, Alamar Blue assay, live/dead assay, immunofluorescence staining, and scanning electron microscopy were used to evaluate the outcome. RESULTS: Results showed that coated membranes maintained the original morphology of nanofibers. After coating with IBPs, the water contact angle of the membrane surfaces varied from 92.38 ± 0.67 degrees to 20.16 ± 0.81 degrees. RPE cells seeded on IBP-coated membranes showed the highest viability at all time points (Day 1, p < 0.05; Day 3, p < 0.01; Days 7 and 14, p < 0.001). The proliferation rate of RPE cells on uncoated poly(ε-caprolactone) (PCL) membranes was significantly lower than that of IBP-coated membranes (p < 0.001). SEM images showed a well-organized hexa/polygonal monolayer of RPE cells on IBP-coated membranes. RPE cells proliferated rapidly, contacted, and became confluent. RPE cells formed a tight adhesion with nanofibers under high-magnification SEM. Our findings confirmed that the IBP-coated PCL membrane improved the attachment, proliferation, and viability of RPE cells. In addition, in this study, we used serum-free culture for RPE cells and short IBPs without immunogenicity to prevent graft rejection and immunogenicity during transplantation. CONCLUSIONS: These results indicated that the biomimic BM-IBP-RPE nanofibrous graft might be a new, practicable approach to increase the success rate of RPE cell transplantation.

The three frontlines against COVID-19: Brain, Behavior, and Immunity.

The pandemic outbreak of coronavirus disease 2019 (COVID-19) is raising global anxiety and fear of both real and perceived health threat from the virus. Overwhelming evidence shows infected patients experiencing neuropsychiatric complications, suggesting that the "psychoneuroimmunity" model might be beneficial in understanding the impact of the virus. Therefore, this Special Issue on "Immunopsychiatry of COVID-19 Pandemic" was launched immediately after the pandemic was declared, with the first paper accepted on the March 25th, 2020. A total of ninety-three papers were accepted, the last one was on the July 10th, 2020 when the initial acute phase started declining. The papers of this Special Issue have illuminated the social impact, psychopathology, neurological manifestation, immunity responses, and potential treatments and prevention on COVID-19. For example, anxiety disorders, mood disorders, and suicidal ideation are most common psychiatric manifestations. COVID-19 infection can have central and/or peripheral nervous system symptoms, including headache, sleep disorders, encephalopathy, and loss of taste and smell. A "three-steps" Neuro-COVID infection model (neuro-invasion, clearance and immune response) was established. The current therapeutic interventions for COVID-19 include supportive intervention, immunomodulatory agents, antiviral therapy, and plasma transfusion. Psychological support should be implemented, improving the psychological wellbeing, as well as to enhance psychoneuroimmunity against COVID-19.

A Review of the Global Impact of the COVID-19 Pandemic on Public Mental Health, with a Comparison Between the USA, Australia, and Poland with Taiwan and Thailand.

Coronavirus may have a negative impact not only on physical, but also on mental wellbeing. Despite the different approaches of countries to stop the spread of the virus and different infection rates, the dynamically developing pandemic has already affected the entire world. The consequences of the coronavirus for our mental health can be divided into those related to strategies for the prevention of infection, like isolation, quarantine, limitation of social contacts, and remote work, and those related to the direct impact of infection on our nervous system. This review aims to highlight the global effects of the Coronavirus Disease 2019 (COVID-19) pandemic on public mental health following social restrictions, to identify how infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may have direct neurophysiological effects and to compare the impact on public mental health between the USA, Australia, and Poland with Taiwan and Thailand.

The Immunotherapy for Colorectal Cancer, Lung Cancer and Pancreatic Cancer.

Immunotherapy is a novel anti-cancer method which employs a different mechanism to conventional treatment. It has become a significant strategy because it provides a better or an alternative option for cancer patients. Recently, immunotherapy has been increasingly approved for the treatment of cancer; however, it has various limitations; for instance, it is only suitable for specific patients, the response rate is still low in most cases, etc. Colorectal cancer, lung cancer and pancreatic cancer are known as three major death-causing cancers in most countries. In this review, we discuss immunotherapeutic treatment for these three cancers, and consider the option, prospects and limitations of immunotherapy. The development of immunotherapy should focus on the discovery of biomarkers to screen suitable patients, new targets on tumors, neoadjuvant immunotherapy and the combination of immunotherapy with conventional therapeutic methods. We can expect that immunotherapy potentially will develop as one of the best therapies for patients with advanced cancer or poor responses to traditional methods.

Potential Therapeutic Approaches Against Brain Diseases Associated with Cytomegalovirus Infections.

Cytomegalovirus (CMV) is one of the major human health threats worldwide, especially for immunologically comprised patients. CMV may cause opportunistic infections, congenital infections, and brain diseases (e.g., mental retardation and glioblastoma). The etiology of brain diseases associated with human CMV (HCMV) infections is usually complex and it is particularly difficult to treat because HCMV has a life-long infection in its hosts, high mutation rate, and latent infections. Moreover, it is almost impossible to eradicate latent viruses in humans. Although there has been progress in drug discovery recently, current drugs used for treating active CMV infections are still limited in efficacy due to side effects, toxicity, and viral resistance. Fortunately, letermovir which targets the HCMV terminase complex rather than DNA polymerase with fewer adverse reactions has been approved to treat CMV infections in humans. The researchers are focusing on developing approaches against both productive and latent infections of CMV. The gene or RNA targeting approaches including the external guide sequences (EGSs)-RNase, the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system and transcription activator-like effector nucleases (TALENs) are being investigated to remove acute and/or latent CMV infections. For the treatment of glioblastoma, vaccine therapy through targeting specific CMV antigens has improved patients' survival outcomes significantly and immunotherapy has also emerged as an alternative modality. The advanced research for developing anti-CMV agents and approaches is promising to obtain significant outcomes and expecting to have a great impact on the therapy of brain diseases associated with CMV infections.

Alcohol Addiction, Gut Microbiota, and Alcoholism Treatment: A Review.

Alcohol addiction is a leading risk factor for personal death and disability. In 2016, alcohol use caused 2.2% of female deaths and 6.8% of male deaths, and disability-adjusted life years (DALYs) were 2.3% in female and 8.9% in male. Individuals with alcohol use disorder are at high risk of anxiety, depression, impaired cognition performance, and illicit drug use and are comorbid with liver disease, such as alcoholic hepatitis and liver cirrhosis, which is a major cause of personal death and disability worldwide. Psychological interventions, such as cognitive behavior therapy and motivational interviewing, as well as medical treatments, such as disulfiram, naltrexone, acamprosate, and nalmefene, are used for the treatment of alcohol addiction in Europe and the United States. However, the effect of current interventions is limited, and the need for additional interventions is substantial. Alcohol use impairs the intestinal barrier and causes changes to the intestinal permeability as well as the gut microbiota composition. Emerging studies have tried to reveal the role of the gut-brain axis among individuals with alcohol use disorder with or without alcohol liver disease. Bacterial products penetrate the impaired intestinal barrier and cause central inflammation; changes to the gut microbiota impair enterohepatic circulation of bile acids; alcohol abuse causes shortage of vital nutrients such as thiamine. Several studies have suggested that probiotics, through either oral administration or fecal microbiota transplantation, increased intestinal levels of potentially beneficial bacteria such as bifidobacteria and lactobacilli, improving the levels of liver-associated enzymes in patients with mild alcoholic hepatitis, and demonstrating beneficial psychotropic effects on anxiety and depression. In addition to medications for alcohol addiction, gene editing therapy such as clustered regularly interspaced short palindromic repeats (CRISPRs) may be another potential research target. Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), which are associated with ADH and ALDH genes, are major enzymes involved in alcohol metabolism, and gene editing approaches may have the potential to directly modify specific genes to treat alcoholism caused by genetic defects. Further research is needed to study the effect of the combined treatment for alcohol addiction.

Opioid Addiction, Genetic Susceptibility, and Medical Treatments: A Review.

Opioid addiction is a chronic and complex disease characterized by relapse and remission. In the past decade, the opioid epidemic or opioid crisis in the United States has raised public awareness. Methadone, buprenorphine, and naloxone have proven their effectiveness in treating addicted individuals, and each of them has different effects on different opioid receptors. Classic and molecular genetic research has provided valuable information and revealed the possible mechanism of individual differences in vulnerability for opioid addiction. The polygenic risk score based on the results of a genome-wide association study (GWAS) may be a promising tool to evaluate the association between phenotypes and genetic markers across the entire genome. A novel gene editing approach, clustered, regularly-interspaced short palindromic repeats (CRISPR), has been widely used in basic research and potentially applied to human therapeutics such as mental illness; many applications against addiction based on CRISPR are currently under research, and some are successful in animal studies. In this article, we summarized the biological mechanisms of opioid addiction and medical treatments, and we reviewed articles about the genetics of opioid addiction, the promising approach to predict the risk of opioid addiction, and a novel gene editing approach. Further research on medical treatments based on individual vulnerability is needed.

TSG-6 secreted by bone marrow mesenchymal stem cells attenuates intervertebral disc degeneration by inhibiting the TLR2/NF-κB signaling pathway.

Inflammation has been correlated with intervertebral disc degeneration (IDD). Recent evidence suggests that TNF-α-stimulated gene 6 protein (TSG-6) secreted by bone marrow mesenchymal stem cells (BMSCs) displays a remarkable ability to inhibit inflammatory processes in a variety of diseases. However, it is unknown whether BMSCs exert their therapeutic effect against IDD by secreting TSG-6. Here we investigated the effects of BMSCs and TSG-6 on IDD and explored the possible underlying mechanisms in vitro and in vivo. We found that BMSCs and TSG-6 reduced the expression of MMP-3 and MMP-13, and increased the expression of collagen II and aggrecan in the IL-1ß-treated nucleus pulposus cells (NPCs), but the protective effects of BMSCs and TSG-6 were attenuated when TSG-6 expression was silenced. We also found that the activation of the TLR2/NF-κB pathway was inhibited by BMSCs and TSG-6. The levels of IL-6 and TNF-α in the degenerated NPCs were reduced and the proliferation of IL-1ß-treated NPCs was increased in the presence of BMSCs and TSG-6. Furthermore, in vivo experiments showed that BMSCs and TSG-6 restored the MRI T2-weighted signal intensity and increased collagen II and aggrecan expression in the degenerated nucleus pulposus (NP) tissues. Finally, our results showed that BMSCs and TSG-6 downregulated the TLR2/NF-κB signaling and reduced the expression of MMPs and inflammatory cytokines in the degenerated NP tissues. The present study is the first to demonstrate the involvement of TLR2/NF-κB pathway in the potential anti-IDD therapeutic effect of TSG-6, and the results provide new insight into the beneficial effect of BMSCs in the treatment of IDD.

NLRP3/ASC-mediated alveolar macrophage pyroptosis enhances HMGB1 secretion in acute lung injury induced by cardiopulmonary bypass.

Our previous study showed that high levels of HMGB1 existed in rats following cardiopulmonary bypass (CPB)-induced acute lung injury (ALI) and neutralization of high-mobility group box 1(HMGB1) reduced CPB-induced ALI. However, the mechanism by which CPB increases HMGB1 secretion is unclear. Recent studies have shown that inflammasome-mediated cell pyroptosis promotes HMGB1 secretion. This study aimed to investigate the relationship between inflammasome-mediated pyroptosis and HMGB1 in CPB-related ALI. We employed oxygen-glucose deprivation (OGD)-induced alveolar macrophage (AM) NR8383 pyroptosis to measure HMGB1 secretion. We found that OGD significantly increased the levels of caspase-1 cleaved p10, IL-1ß and ASC expression, caspase-1 activity and the frequency of pyroptotic AM, and promoted the cytoplasm transportation and secretion of HMGB1, which were significantly mitigated by ASC silencing or pre-treatment with glyburide (a Nlrp3 inhibitor) in AM. CPB also increased the expression levels of Nlrp3, ASC, caspase-1 P10, and IL-1ß, and the percentages of AM pyroptosis in the lungs of experimental rats accompanied by increased levels of serum and bronchoalveolar lavage fluid (BALF) HMGB1. Treatment with glyburide significantly mitigated the CPB-increased ASC, caspase-1 p10 and IL-1ß expression, and the percentages of AM pyroptosis in the lungs, as well as the levels of HMGB1 in serum and BALF in rats. Therefore, our data indicated that the Nlrp3/ASC-mediated AM pyroptosis increased HMGB1 secretion in ALI induced by CPB. These findings may provide a therapeutic strategy to reduce lung injury and inflammatory responses during CPB.

Diagnostic Accuracy of Serum CA19-9 in Patients with Cholangiocarcinoma: A Systematic Review and Meta-Analysis.

BACKGROUND Cholangiocarcinoma (CCA) is a relatively rare cancer worldwide; however, its incidence is extremely high in Asia. Numerous studies reported that serum carbohydrate antigen 19-9 (CA19-9) plays a role in the diagnosis of CCA patients. However, published data are inconclusive. The aim of this meta-analysis was to provide a systematic review of the diagnostic performance of CA19-9 for CCA. MATERIAL AND METHODS We searched the public databases including PubMed, Web of Science, Embase, Chinese National Knowledge Infrastructure (CNKI), and WANFANG databases for articles evaluating the diagnostic accuracy of serum CA19-9 to predict CCA. The diagnostic sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and summary receiver operating characteristic curve (SROC) were pooled by Meta-DiSc 1.4 software. RESULTS A total of 31 articles met the inclusion criteria, including 1,264 patients and 2,039 controls. The pooled SEN, SPE, PLR, NLR, and DOR were 0.72 (95% CI: 0.70-0.75), 0.84 (95% CI: 0.82-0.85), 4.93 (95% CI, 3.67-6.64), 0.35 (95%CI, 0.30-0.41), and 15.10 (95% CI, 10.70-21.32), respectively. The area under SROC curve was 0.8300. The subgroup analyses based on different control type, geographical location, and sample size revealed that the diagnostic accuracy of CA19-9 tends to be same in different control type, but showed low sensitivity in European patients and small size group. CONCLUSIONS Serum CA19-9 is a useful non-invasive biomarker for CCA detection and may become a clinically useful tool to identify high-risk patients.

Enhancement of Oral Bioavailability of Curcumin by a Novel Solid Dispersion System.

The objective of this study was to improve the solubility and bioavailability of curcumin by a new curcumin dripping pills (Cur-DPs) formulation using melt mixing methods. The optimal formulation consisted of Polyethoxylated 40 hydrogenated castor oil (Cremophor RH40), Poloxamer 188, and Polyethylene glycol 4000 (PEG 4000). Differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier-transform infrared spectroscopy (FT-IR) were used to verify the forming of Cur-DPs. All the physical characterization information proved the formation of Cur-DPs, and the results demonstrated the superiority of the dripping pills in dissolution rates. The pharmacokinetic study of Cur-DPs was performed in rats compared to the pure curcumin suspension. The oral bioavailability of poorly water-soluble curcumin was successfully improved by CUR-DPs. And the stability of prepared Cur-DP was also in a good state in 3 months. These results identified the Cur-DPs was an effective new approach for pharmaceutical application.

[Association of choroidal thickness with diabetic retinopathy at different stages].

OBJECTIVE: To explore the association of choroidal thickness variations in type 2 diabetes mellitus (T2DM) patients with diabetic retinopathy (DR) at different stages. METHODS: A total of 161 patients with T2DM were included in this study, from October 2012 to June 2014. According to Early Treatment Diabetic Retinopathy Study (ETDRS) criteria, the patients were divided into 5 groups: non-DR without diabetic macular edema (DME) group(DR-/DME- group, 45 eyes), nonproliferative diabetic retinopathy (NPDR) without DME group(NPDR+/DME- group, 58 eyes), proliferative diabetic retinopathy (PDR) without DME group (PDR+/DME- group, 12 eyes), NPDR with DME group (NPDR+/DME+ group, 41 eyes), PDR with DME group (PDR+/DME+ group, 5 eyes). Meanwhile, 60 normal subjects were enrolled as the control group. All study subjects received optical coherence tomography enhanced depth imaging (EDI-OCT) examination to detect and compare subfoveal choroidal thickness at different stages of DR. RESULTS: Mean SFCT was (271 ± 36), (270 ± 35), (262 ± 38), (244 ± 36), (229 ± 35) µm respectively in control, DR-/DME-, NPDR+/DME-, PDR+/DME-, NPDR+/DME+ groups. The SFCTs of PDR+/DME- and NPDR+/DME+ group were statistically lower than that of control group (P=0.004, P=0.001). The SFCT of PDR+/DME- group was lower than that of DR-/DME- group (P=0.003), and there was also a significant difference of SFCT between NPDR+/DME+ and NPDR+/DME- group (P=0.001). There was linear correlation between SFCT and the logMAR best-corrected visual acuity (r=0.397, P<0.01), but the SFCT was independent of diabetic duration, fasting blood glucose, HbA1c, axial length, diastolic blood pressure (DBP) and systolic blood pressure SBP (r=-0.024, 0.159, 0.089, 0.036, 0.143, 0.057, all P>0.05). There was no significant difference of SFCT among different DME types (F=0.071, P>0.05). CONCLUSION: The SFCT decreased with increasing severity of DR. To monitor the SFCT in T2DM patients may be helpful to evaluate the severity of DR and provide a new treatment conception.

Tumor suppressor miR-361-3p inhibits prostate cancer progression through Gli1 and AKT/mTOR signaling pathway.

BACKGROUND: The primary challenge in prostate cancer (PCa) is tumor metastasis, which seriously affects the survival time of patients. Growing evidence suggests that microRNAs play a crucial regulatory role in various malignancies and that the tumor suppressor miR-361-3p is responsible for regulating migration, proliferation, and invasion in different cancer types. However, the underlying regulatory mechanism of miR-361-3p in PCa remains unknown. METHODS: The expression of miR-361-3p in PCa cells was analyzed using quantitative real time-polymerase chain reaction. The clinical utility of miR-361-3p in PCa was evaluated using in vitro assays. The mechanism of action of miR-361-3p was investigated using western blotting, luciferase reporter assays, immunofluorescence, and rescue studies. RESULTS: The function, invasiveness, migration, and proliferation of PCa cells, as well as epithelial-mesenchymal transition (EMT), were aided by the downregulation of miR-361-3p, whereas its overexpression exerted the opposite effect. Repression of glioma-associated oncogene homolog 1 (Gli1) expression by miR-361-3p led to activation of the protein kinase B/mammalian target of rapamycin (AKT/mTOR) signaling pathway, triggering EMT and promoting PCa metastasis. CONCLUSIONS: Downregulation of miR-361-3p along the Gli1 axis promoted tumor malignancy. Collectively, the results of this study imply that miR-361-3p has the potential to be both a biomarker and therapeutic target in PCa.

Challenges and Recent Advancements in COVID-19 Vaccines.

Vaccination is the most effective method for the prevention of COVID-19 caused by SARS-CoV-2, which is still a global epidemic. However, the evolution of SARS-CoV-2 is so rapid that various variants, including the Alpha, Beta, Gamma, Delta, and Omicron variants, have emerged, lowering the protection rate of vaccines and even resulting in breakthrough infections. Additionally, some rare but severe adverse reactions induced by COVID-19 vaccines may raise safety concerns and hinder vaccine promotion; however, clinical studies have shown that the benefits of vaccination outweigh the risks caused by adverse reactions. Current vaccines approved with emergency use authorization (EUA) were originally adaptive for adults only, and infants, children, and adolescents are not included. New-generation vaccines are needed to overcome the challenges of limited adaptive age population, breakthrough infection (mainly due to virus variant emergencies), and critical adverse reactions. Fortunately, some advances in COVID-19 vaccines have been obtained regarding enlarged adaptive populations for clinical applications, such as the Pfizer/BioNTech vaccine and the Moderna vaccine. In this article, we provide a review on the challenges and recent advancements in COVID-19 vaccines. The development of next-generation COVID-19 vaccines should lay emphasis on the expansion of adaptive age populations in all individuals, the induction of immune responses to viral variants, the avoidance or alleviation of rare but potentially critical adverse reactions, and the discovery of subunit vaccines with adjuvants encapsulated in nanoparticles.

Trauma-related guilt as a mediator between post-traumatic stress disorder and suicidal ideation.

Background: As a mental health issue, suicide is a growing global concern, with patients who have post-traumatic stress disorder (PTSD) being at particularly high risk. This study aimed to investigate whether the link between PTSD and suicidal ideation is mediated by trauma-related guilt. Methods: Data were obtained from Wave 1, Time 1 (November 2016), and Time 2 (March 2017) of the National Survey for Stress and Health (NSSH) in Japan. The NSSH is an online longitudinal survey conducted on Japan's national population aged 18 years and older. The cumulative response rate of the survey was 66.7% at Time 2. A total of 1,005 patients with PTSD were included for analyses. The severity of PTSD symptoms was assessed with PTSD DSM-5 Checklist, and the trauma-related guilt were assessed using the two subscales (hindsight-bias/responsibility and global guilt scale) of the trauma-related guilt inventory (TRGI). Suicidal ideation was evaluated using the suicidal ideation attributes scale (SIDAS). Pearson's correlation was used to investigate the associations among PTSD symptoms, TRGI scores, and SIDAS scores. Causal mediation analysis was applied to evaluate the causal relationship between PTSD, trauma-related guilt, and suicidal ideation. Results: Pearson's correlation did not show patients' age, gender, and household income significantly associated with SIDAS scores. On the other hand, severities of PTSD symptoms (r = 0.361, p < 0.001) and trauma-related guilt (r = 0.235, p < 0.001) were positively associated with SIDAS scores. After adjusting for age, gender, and household income, the mediation analysis revealed that trauma-related guilt significantly mediates the effects of PTSD symptoms on suicidal ideation. Conclusion: Our results implied that trauma-related guilt may represent a critical link between PTSD and suicidal ideation, which may be a noteworthy target for therapeutic intervention.

Point-of-Care Testing for Infectious Diseases Based on Class 2 CRISPR/Cas Technology.

The early detection of infectious diseases and microorganisms is critical for effective disease treatment, control, and prevention. Currently, nucleic acid testing and antigen-antibody serum reaction are the two methods most commonly used for the detection of infectious diseases. The former is highly accurate, specific, and sensitive, but it is time-consuming, expensive, and has special technician and instrument requirements. The latter is rapid and economical, but it may not be accurate and sensitive enough. Therefore, it is necessary to develop a quick and on-site diagnostic test for point-of-care testing (POCT) to enable the clinical detection of infectious diseases that is accurate, sensitive, convenient, cheap, and portable. Here, CRISPR/Cas-based detection methods are detailed and discussed in depth. The powerful capacity of these methods will facilitate the development of diagnostic tools for POCT, though they still have some limitations. This review explores and highlights POCT based on the class 2 CRISPR/Cas assay, such as Cas12 and Cas13 proteins, for the detection of infectious diseases. We also provide an outlook on perspectives, multi-application scenarios, clinical applications, and limitations for POCT based on class 2 CRISPR/Cas technology.

Associations between frontal lobe activity and depressive symptoms in patients with major depressive disorder receiving rTMS treatment: a near-infrared spectroscopy study.

Introduction: The effects of repetitive transcranial magnetic stimulation (rTMS) on the left dorsolateral prefrontal cortex (DLPFC) in patients with major depressive disorder (MDD) have been proved to have antidepressant effects. However, the absence of biomarkers to assess treatment response remains a challenge. This research aims to explore the relationship between frontal lobe activity, measured using near infrared spectroscopy (NIRS), and changes in symptoms among MDD patients following rTMS treatment. Methods: A total of 26 MDD patients underwent 20 sessions of 10 Hz rTMS targeting the left DLPFC. NIRS was used to measure frontal lobe activity during a verbal fluency test at baseline, after 10 rTMS sessions, and after 20 rTMS sessions. Responders were defined as individuals with more than a 50% reduction in symptoms based on the 21-item Hamilton Depression Rating Scale after 20 rTMS sessions. Results: Among the 14 responders, an increase in frontal lobe activity was significantly correlated with improvements in depressive symptoms following 10 (p = 0.0001) and 20 rTMS sessions (p = 0.007). Additionally, frontal lobe activity after 10 rTMS sessions was significantly associated with symptom improvement after 20 sessions (p = 0.001). These associations were not observed among non-responders. Conclusion: The findings from this study indicate distinct patterns of frontal lobe activity between responders and non-responders to rTMS treatment, suggesting that NIRS has the potential to serve as a biomarker for monitoring treatment response in MDD patients undergoing rTMS.

Aberrant Histone Modification of TNFAIP3, TLR4, TNIP2, miR-146a, and miR-155 in Major Depressive Disorder.

Activated toll-like receptor (TLR) signaling has been well investigated in major depressive disorder (MDD). We previously reported that TNFAIP3, TLR4, TNIP2, miR-146a, and miR-155 play important roles in regulating the toll-like receptor 4 (TLR4) signaling pathway and may serve as novel targets in the pathogenesis of MDD. Recently, aberrant histone modification has been implicated in several psychiatric disorders, including schizophrenia and mood disorder; the most thoroughly studied modification is histone 3 lysine 4 tri-methylation (H3K4me3). In this work, we aimed to explore H3K4me3 differences in the promotors of genes encoding the abovementioned factors in patients with MDD, and whether they were altered after antidepressant treatment. A total of 30 MDD patients and 28 healthy controls were recruited. Peripheral blood mononuclear cells (PBMCs) were collected. The levels of H3K4me3 in the promoters of TNFAIP3, TLR4, TNIP2, miR-146a, and miR-155 were measured through chromatin immunoprecipitation (ChIP) followed by DNA methylation assay. Analysis of covariance was used to evaluate between-group differences after adjusting for age, sex, BMI, and smoking. In comparison with healthy controls, patients with MDD showed significantly lower H3K4me3 levels in the promoters of TNFAIP3, TLR4, TNIP2, miR-146a, and miR-155 in PBMCs. These levels were not significantly altered after completion of a 4-week antidepressant treatment. To explore the association between depression severity and H3K4me3 levels, a multiple linear regression model was generated. The results revealed that levels of H3K4me3 in the TNIP2 promoters a negative correlation with the 17-item Hamilton Depression Rating Scale (HAND-17) score, whereas that of TLR4 had a positive correlation with this score. The present results suggest that decreased H3K4me3 levels in the promoters of the genes encoding TNFAIP3, TLR4, miR-146a, miR-155, and TNIP2 are involved in psychopathology of major depressive disorder.

NIRS-aided differential diagnosis among patients with major depressive disorder, bipolar disorder, and schizophrenia.

BACKGROUND: To establish a clinically applicable neuroimaging-guided diagnostic support system that uses near-infrared spectroscopy (NIRS) for differential diagnosis at the individual level among major depressive disorder (MDD), bipolar disorder (BPD), and schizophrenia (SZ). METHODS: A total of 192 participants were recruited, including 40 patients with MDD, 38 patients with BPD, 65 patients with SZ, and 49 healthy individuals. We analyzed the spatiotemporal characteristics of hemodynamic responses in the frontotemporal cortex during a verbal fluency test (VFT) measured by NIRS to assess the accuracy of single-subject classification for differential diagnosis among the three psychiatric disorders. The optimal threshold of the frontal centroid value (54 seconds) was utilized on the basis of the findings of the Japanese study. RESULTS: The application of the optimal threshold of the frontal centroid value (54 seconds) allowed for the accurate differentiation of patients with unipolar MDD (72.5%) from BPD (78.9%) or SZ (84.6%). CONCLUSION: These results suggest that the NIRS-aided differential diagnosis of major psychiatric disorders can be a promising biomarker in Taiwan. Future multi-site studies are needed to validate our findings.

The Clinical Observation of Inflammation Theory for Depression: The Initiative of the Formosa Long COVID Multicenter Study (FOCuS).

There is growing evidence that the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with increased risks of psychiatric sequelae. Depression, anxiety, cognitive impairments, sleep disturbance, and fatigue during and after the acute phase of COVID-19 are prevalent, long-lasting, and exerting negative consequences on well-being and imposing a huge burden on healthcare systems and society. This current review presented timely updates of clinical research findings, particularly focusing on the pathogenetic mechanisms underlying the neuropsychiatric sequelae, and identified potential key targets for developing effective treatment strategies for long COVID. In addition, we introduced the Formosa Long COVID Multicenter Study (FOCuS), which aims to apply the inflammation theory to the pathogenesis and the psychosocial and nutrition treatments of post-COVID depression and anxiety.