Green tea extract ameliorates macrophage-driven emphysematous lesions in chronic obstructive pulmonary disease induced by cigarette smoke condensate.

Chronic obstructive pulmonary disease (COPD) is an important lung disease characterized by complicated symptoms including emphysema. We aimed to explore the mechanisms underlying the protective effect of green tea extract (GTE) on cigarette smoke condensate (CSC)-induced emphysema by demonstrating the reduction of macrophage-induced protease expression through GTE treatment in vivo and in vitro. Mice were intranasally administered 50 mg/kg CSC once a week for 4 weeks, and doses of 100 or 300 mg/kg GTE were administered orally once daily for 4 weeks. GTE significantly reduced macrophage counts in bronchoalveolar lavage fluid and emphysematous lesions in lung tissues in CSC-exposed mice. In addition, GTE suppressed CSC-induced extracellular signal-regulated kinase (ERK)/activator protein (AP)-1 phosphorylation followed by matrix metalloproteinases (MMP)-9 expression as revealed by western blotting, immunohistochemistry, and zymography in CSC-instilled mice. These underlying mechanisms related to reduced protease expression were confirmed in NCI-H292 cells stimulated by CSC. Taken together, GTE effectively inhibits macrophage-driven emphysematous lesions induced by CSC treatment, and these protective effects of GTE are closely related to the ERK/AP-1 signaling pathway, followed by a reduced protease/antiprotease imbalance. These results suggest that GTE can be used as a supplementary agent for the prevention of emphysema progression in COPD patients.

Early Hospice Consultation Team Engagement for Cancer Pain Relief: A Case Report.

This case report explores the challenges and complexities associated with opioid management of cancer pain, emphasizing the importance of early involvement of a hospice consultation team and the adoption of a multidisciplinary approach to care. A 56-year-old man with advanced pancreatic cancer experienced escalating pain and inappropriate opioid prescriptions, highlighting the shortcomings of traditional pain management approaches. Despite procedural intervention by the attending physician and increased opioid dosages, the patient's condition deteriorated. Subsequently, the involvement of a hospice consultation team, in conjunction with collaborative psychiatric care, led to an overall improvement. The case underscores the necessity of early hospice engagement, psychosocial assessments, and collaborative approaches in the optimization of patient-centered palliative care.

Oral bioavailability and egg drug residue of lincomycin in laying hens after different treatment.

Lincomycin (LCM) is an antibiotic used to treat severe bacterial infections in livestock and companion animals. In this study, we aimed to investigate the oral bioavailability of LCM with PK data after IV and PO administration and to compare differences in drug residue patterns in eggs. To ensure food safety, an additional study on egg residue was conducted using 3 different commercial LCM drugs. For bioavailability study, laying hens were divided into oral and intravenous (n = 8/group) groups and received single dose (10 mg/kg) of LCM. The limits of quantification for LCM were 0.729 µg/mL and 0.009 mg/kg in plasma and eggs, respectively. The oral group exhibited a significantly lower average serum drug concentration than the IV group, with a bioavailability of 2.6%. Furthermore, the egg residue profiles confirmed reduced systemic drug exposure after oral administration. For the commercial LCM drug egg residue experiment, laying hens were divided into low- and high-dose groups (n = 12/group) for each drug and treated with the recommended dosage and administration method for each respective drug. The eggs were collected and analyzed until 14 d after the last drug treatment. Despite differences in the LCM content and formulation among commercial drugs, all the tested commercial drugs showed average concentrations below the MRL in eggs within approximately 3 d after the last drug treatment. In this study, we have confirmed that LCM has a low oral absorption rate in laying hens, and this was consistent with the findings from the egg residue profiles. Further studies are requested to elucidate the exact reasons for evidently low oral drug absorption in laying hens.

Korean Red Ginseng suppresses emphysematous lesions induced by cigarette smoke condensate through inhibition of macrophage-driven apoptosis pathways.

Background: Cigarette smoke is generally accepted as a major contributor to chronic obstructive pulmonary disease (COPD), which is characterized by emphysematous lesions. In this study, we investigated the protective effects of Korean Red Ginseng (KRG) against cigarette smoke condensate (CSC)-induced emphysema. Methods: Mice were instilled with 50 mg/kg of CSC intranasally once a week for 4 weeks, KRG was administered to the mice once daily for 4 weeks at doses of 100 or 300 mg/kg, and dexamethasone (DEX, positive control) was administered to the mice once daily for 2 weeks at 3 mg/kg. Results: KRG markedly decreased the macrophage population in bronchoalveolar lavage fluid and reduced emphysematous lesions in the lung tissues. KRG suppressed CSC-induced apoptosis as revealed by terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling staining and Caspase 3 immunohistochemistry. Additionally, KRG effectively inhibited CSC-mediated activation of Bcl-2-associated X protein/Caspase 3 signaling, followed by the induction of cell survival signaling, including vascular endothelial growth factor/phosphoinositide 3-kinase/protein kinase B in vivo and in vitro. The DEX group also showed similar improved results in vivo and in vitro. Conclusion: Taken together, KRG effectively inhibits macrophage-mediated emphysema induced by CSC exposure, possibly via the suppression of pro-apoptotic signaling, which results in cell survival pathway activation. These findings suggest that KRG has therapeutic potential for the prevention of emphysema in COPD patients.

Korean red ginseng suppresses mitochondrial apoptotic pathway in denervation-induced skeletal muscle atrophy.

Background: Skeletal muscle denervation leads to motor neuron degeneration, which in turn reduces muscle fiber volumes. Recent studies have revealed that apoptosis plays a role in regulating denervation-associated pathologic muscle wasting. Korean red ginseng (KRG) has various biological activities and is currently widely consumed as a medicinal product worldwide. Among them, ginseng has protective effects against muscle atrophy in in vivo and in vitro. However, the effects of KRG on denervation-induced muscle damage have not been fully elucidated. Methods: We induced skeletal muscle atrophy in mice by dissecting the sciatic nerves, administered KRG, and then analyzed the muscles. KRG was administered to the mice once daily for 3 weeks at 100 and 400 mg/kg/day doses after operation. Results: KRG treatment significantly increased skeletal muscle weight and tibialis anterior (TA) muscle fiber volume in injured areas and reduced histological alterations in TA muscle. In addition, KRG treatment reduced denervation-induced apoptotic changes in TA muscle. KRG attenuated p53/Bax/cytochrome c/Caspase 3 signaling induced by nerve injury in a dose-dependent manner. Also, KRG decreases protein kinase B/mammalian target of rapamycin pathway, reducing restorative myogenesis. Conclusion: Thus, KRG has potential protective role against denervation-induced muscle atrophy. The effect of KRG treatment was accompanied by reduced levels of mitochondria-associated apoptosis.

Green tea extract suppresses airway inflammation via oxidative stress-driven MAPKs/MMP-9 signaling in asthmatic mice and human airway epithelial cells.

Introduction: The anti-inflammatory effect of green tea extract (GTE) has been confirmed in asthmatic mice, however, the pharmacological mechanism is not fully elucidated. Methods: To investigate the therapeutic efficacy of GTE in asthma and identify specific pathways, murine model of allergic asthma was established by ovalbumin (OVA) sensitization and the challenge for 4 weeks, with oral treatment using GTE and dexamethasone (DEX). Inflammatory cell counts, cytokines, OVA-specific IgE, airway hyperreactivity, and antioxidant markers in the lung were evaluated. Also, pulmonary histopathological analysis and western blotting were performed. In vitro, we established the model by stimulating the human airway epithelial cell line NCI-H292 using lipopolysaccharide, and treating with GTE and mitogen-activated protein kinases (MAPKs) inhibitors. Results: The GTE100 and GTE400 groups showed a decrease in airway hyperresponsiveness and the number of inflammatory cells in the bronchoalveolar lavage fluid (BALF) compared to the OVA group. GTE treatment also reduced interleukin (IL)-13, IL-5, and IL-4 levels in the BALF, and OVA-specific immunoglobulin E levels in the serum compared to those in the OVA group. GTE treatment decreased OVA-induced mucus secretion and airway inflammation. In addition, GTE suppressed the oxidative stress, and phosphorylation of MAPKs, which generally occurs after exposure to OVA. GTE administration also reduced matrix metalloproteinase-9 activity and protein levels. Conclusion: GTE effectively inhibited asthmatic respiratory inflammation and mucus hyperproduction induced by OVA inhalation. These results suggest that GTE has the potential to be used for the treatment of asthma.

Anti-hyperglycemic effects of Cissus quadrangularis extract via regulation of gluconeogenesis in type 2 diabetic db/db mice.

Introduction: Cissus quadrangularis is a vining plant widely used as a traditional herbal remedy for various ailments. In this study, the therapeutic effects of C. quadrangularis extract (CQR-300) on type 2 diabetes mellitus (T2DM) were investigated in a leptin receptor-mutated db/db mouse model. Methods: CQR-300 was orally administered to db/db mice (n = 6/group) at different doses (50, 100, and 200 mg/kg) for 8 weeks. Blood glucose levels and oral glucose tolerance were assessed using the AccuCheck glucometer. Enzyme-linked immunosorbent assay was performed to evaluate insulin and hemoglobin A1c (HbA1c) levels in the blood of db/db mice. Liver and pancreatic tissues from db/db mice were examined by hematoxylin and eosin (H&E) and immunohistochemical staining. The protein levels of gluconeogenesis-, lipogenesis-, and oxidative stress-related factors were evaluated using western blotting. Results and discussion: CQR-300 treatment effectively reduced body weight, blood glucose, and insulin levels. HbA1c levels were increased by leptin receptor mutation. Additionally, in the oral glucose tolerance tests, the CQR-300 treated group had a faster blood glucose recovery rate than the db/db group. H&E and Oil red-O staining of the liver showed decreased lipid accumulation in the CQR-300 treated group than the db/db group. Western blot analysis confirmed that CQR-300 effectively inhibited gluconeogenesis, lipogenesis, and oxidative stress-related factors. Our findings suggest that CQR-300 has the potential to be used as a T2DM supplement.

The absence of thioredoxin-interacting protein in alveolar cells exacerbates asthma during obesity.

Obesity is associated with an increased incidence of asthma. However, the mechanisms underlying this association are not fully understood. In this study, we investigated the role of thioredoxin-interacting protein (TXNIP) in obesity-induced asthma. Asthma was induced by intranasal injection of a protease from Aspergillus oryzae in normal diet (ND)- or high fat diet (HFD)-fed mice to investigate the symptoms. We measured TXNIP expression in the lungs of patients with asthma and in ND or HFD asthmatic mice. To explore the role of TXNIP in asthma pathogenesis, we induced asthma in the same manner in alveolar type 2 cell-specific TXNIP deficient (TXNIPCre) mice. In addition, the expression levels of pro-inflammatory cytokines were compared based on TXNIP gene expression in A549 cells stimulated with recombinant human tumor necrosis factor alpha. Compared to ND-fed mice, HFD-fed mice had elevated levels of free fatty acids and adipokines, resulting in high reactive oxygen species levels and more severe asthma symptoms. TXNIP expression was increased in both, asthmatic patients and HFD asthmatic mice. However, in experiments using TXNIPCre mice, despite being TXNIP deficient, TXNIPCre mice exhibited exacerbated asthma symptoms. Consistent with this, in vitro studies showed highest expression levels of pro-inflammatory cytokines in TXNIP-silenced cells. Overall, our findings suggest that increased TXNIP levels in obesity-induced asthma is compensatory to protect against inflammatory responses.

Enhanced Energy Storage in Lithium-Metal Batteries via Polymer Electrolyte Polysulfide-Polyoxide Conetworks.

The present article entails a novel concept of storing extra energy in a multifunctional polymer electrolyte membrane (PEM) beyond the storage capacity of a cathode, which is achieved by so-called "prelithiation" upon simply deep discharging to a low potential range of a lithium-metal electrode (i.e., -0.5 to 0.5 V). This unique extra energy-storage capacity has been realized recently in the PEM consisting of polysulfide-co-polyoxide conetworks in conjunction with succinonitrile and LiTFSI salt that facilitate complexation via ion-dipole interaction of dissociated lithium ions with thiols, disulfide, or ether oxygen of the conetwork. Although ion-dipole complexation may increase the cell resistance, the prelithiated PEM provides excess lithium ions during oxidation (or Li+ stripping) at the Li-metal electrode. Once the PEM network is fully saturated with Li ions, the remaining excess ions can move through the complexation sites at ease, thereby affording not only facile ion transport but also extra ion-storage capacity within the PEM conetwork. Of particular interest is that the lithiated polysulfide-co-polyoxide polymer network-based PEM exhibits a high conductivity of 1.18 × 10-3 S/cm at ambient, which can also store extra energy with a specific capacity of about 150 mAh/g at a 0.1C rate in the PEM voltage range of 0.01-3.5 V in addition to 165 mAh/g at 0.2C of an NMC622 (nickel manganese cobalt oxide) cathode (i.e., 2.5-4.6 V) with a Coulombic efficiency of approximate unity. Moreover, its Li-metal battery assembly with an NMC622 cathode exhibits a very high specific capacity of ∼260 mAh/g at 0.2C in the full battery range of 0.01-5 V, having a higher Li+ transference number of 0.74, suggestive of domination by the lithium cation transport relative to those (0.22-0.35) of organic liquid electrolyte lithium-ion batteries.

Protective Effects of Chestnut (Castanea crenata) Inner Shell Extract in Macrophage-Driven Emphysematous Lesion Induced by Cigarette Smoke Condensate.

Chestnut (Castanea crenata) inner shell extract (CIE), a curative herb in Korea, has diverse pharmacological effects against various diseases including pulmonary fibrosis, asthma, and chronic obstructive pulmonary disease (COPD). However, its molecular mechanisms of anti-emphysematous effects are still not fully elucidated. In the present study, we elucidate the efficacy of CIE against emphysematous lesion progression in a cigarette smoke condensate (CSC)-instilled mice and CSC-stimulated H292 cell line. The mice are administered CSC via intranasal instillation at 7-day intervals for 1 month after 1 week of pretreatment with CIE. CIE (100 or 300 mg/kg) is administered by oral gavage for 1 month. CIE decreased the macrophage count in bronchoalveolar lavage fluid and the severity of emphysematous lesions in lung tissue. Additionally, CIE suppressed the phosphatidylinositol 3-kinase/protein kinase B/nuclear factor kappa B signal pathway and thereby downregulated matrix metalloprotease-9 expression, which was confirmed in CSC-stimulated H292 cells. Thus, CIE effectively inhibited CSC-induced macrophage-driven emphysema progression in airways; this inhibition was associated with the suppression of protease-antiprotease imbalance. Our results propose that CIE has the potential for the alleviation of COPD.

Pharmacokinetic profiles and egg residue patterns of levamisole in laying hens at two dosing rates and two routes of administration.

The levamisole maximum residue limit for edible fat, kidney, and muscle of chickens is 0.01 mg/kg. However, no maximum residue limit has been established for eggs. In the present study, the pharmacokinetic profile and levamisole residue in the eggs from laying hens were investigated using ultra-performance liquid chromatography-tandem mass spectrometry. A single dose of levamisole (30 mg/kg) was administered via the intramuscular or oral route, and an additional egg residue study was performed with 300 or 600 mg/kg commercial LEV drug (30 or 60 mg/kg as levamisole) orally. The limit of quantification was 0.0056 µg/mL and 0.0015 mg/kg for plasma and eggs, respectively. The plasma concentration was below the limit of quantification 10 and 12 h after intramuscular and oral administration, respectively. The half-life of the absorption phase was comparable between the intramuscular and oral routes, which was approximately 1 h, and the mean maximum concentration value was significantly higher in intramuscular (2.29 ± 0.30 µg/mL) than in oral (1.45 ± 0.38 µg/mL) route. The relative oral bioavailability after intramuscular administration was 92.3%. In the egg residue study, dose-dependent area under concentration and maximum concentration were observed after single oral administration of 30 and 60 mg/kg egg residue, and the calculated withdrawal period for both 30 and 60 mg/kg groups based on the positive list system standard (0.01 mg/kg) was 7 d after the treatment.

Green tea extract improves cyclophosphamide-induced immunosuppression in mouse spleen and enhances the immune activity of RAW 264.7 cells.

Cyclophosphamide (CP) is mainly used to treat autoimmune diseases and cancer; however, it damages normal immune cells. Therefore, the effects of chemotherapy on CP are limited. Notably, green tea has been reported to effectively modulate immune function. Here, given the pharmacological properties of green tea, we evaluated the ability of green tea extract (GTE) to restore immunity suppressed by CP in vivo and to activate macrophages in vitro. GTE significantly improved the suppressed immune function, including spleen index and proliferation of spleen T lymphocytes, as revealed by histopathological examination and flow cytometry analysis. Moreover, GTE effectively activated RAW 264.7, as represented by the induction of nitric oxide, reactive oxygen species, and cytokine levels. GTE also increased the phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B in RAW 264.7 cells. In conclusion, GTE ameliorated CP-induced immunosuppression in mice and stimulated immune activity in RAW 264.7 cells, possibly by activating the MAPK signaling pathway. These findings suggest that GTE has the potential to be used as a supplementary agent in chemotherapy for CP.

The Aqueous Leaf Extract of the Medicinal Herb Costus speciosus Suppresses Influenza A H1N1 Viral Activity under In Vitro and In Vivo Conditions.

This study investigated the antiviral activity of aqueous leaf extract of Costus speciosus (TB100) against influenza A. Pretreatment of TB100 in RAW264.7 cells enhanced antiviral activity in an assay using the green fluorescence-expressing influenza A/Puerto Rico/8/1934 (H1N1) virus. The fifty percent effective concentration (EC50) and fifty percent cytotoxic concentration (CC50) were determined to be 15.19 ± 0.61 and 117.12 ± 18.31 µg/mL, respectively, for RAW264.7 cells. Based on fluorescent microscopy, green fluorescence protein (GFP) expression and viral copy number reduction confirmed that TB100 inhibited viral replication in murine RAW264.7 and human A549 and HEp2 cells. In vitro pretreatment with TB100 induced the phosphorylation of transcriptional activators TBK1, IRF3, STAT1, IKB-α, and p65 associated with interferon pathways, indicating the activation of antiviral defenses. The safety and protective efficacy of TB100 were assessed in BALB/c mice as an oral treatment and the results confirmed that it was safe and effective against influenza A/Puerto Rico/8/1934 (H1N1), A/Philippines/2/2008 (H3N2), and A/Chicken/Korea/116/2004 (H9N2). High-performance liquid chromatography of aqueous extracts led to the identification of cinnamic, caffeic, and chlorogenic acids as potential chemicals for antiviral responses. Further confirmatory studies using these acids revealed that each of them confers significant antiviral effects against influenza when used as pretreatment and enhances the antiviral response in a time-dependent manner. These findings suggest that TB100 has the potential to be developed into an antiviral agent that is effective against seasonal influenza.

Inner Shell of the Chestnut (Castanea crenatta) Suppresses Inflammatory Responses in Ovalbumin-Induced Allergic Asthma Mouse Model.

The inner shell of the chestnut (Castanea crenata) contains various polyphenols, which exert beneficial biological effects. Hence, we assessed the anti-inflammatory efficacy of a chestnut inner shell extract (CIE) in ovalbumin (OVA)-induced allergic asthma. We intraperitoneally injected 20 µg of OVA with 2 mg of aluminum hydroxide on days 0 and 14. On test days 21, 22, and 23, the mice were treated with aerosolized 1% (w/v) OVA in saline. CIE was administered orally at 100 and 300 mg/kg on days 18-23. CIE significantly reduced inflammatory cytokines and cells and immunoglobulin-E increased by OVA. Anti-inflammatory efficacy was revealed by reduction of inflammatory cell migration and mucus secretion in lung tissue. Further, CIE suppressed the OVA-induced nuclear factor kappa B (NF-κB) phosphorylation. Accordingly, the expression of cyclooxygenase (COX-2), inducible nitric oxide synthase (iNOS), and matrix metalloproteinase-9 (MMP-9) were decreased sequentially in lung tissues. CIE alleviated OVA-induced airway inflammation by restraining phosphorylation of NF-κB and the sequentially reduced expression of iNOS, COX-2, leading to reduced MMP-9 expression. These results indicate that CIE has potential as a candidate for alleviating asthma.

Korean Red Ginseng Ameliorates Allergic Asthma through Reduction of Lung Inflammation and Oxidation.

Six-year-old red ginseng, which is processed from the whole ginseng root via steaming and drying, has been shown to have preventive effects such as antioxidative, anti-inflammatory, and immunomodulatory. In this study, we evaluated the therapeutic effects of Korean red ginseng (KRG) against ovalbumin (OVA)-induced allergic asthma and the underlying mechanisms involved. We injected 20 µg of OVA on days 0 and 14, and mice were challenged with aerosolized OVA via a nebulizer for 1 h on days 21, 22, and 23. KRG was administered at 100 and 300 mg/kg from days 18 to 23. The KRG-treated mice showed significant reductions in their airway hyperresponsiveness, production of reactive oxygen species (ROS), and the number of inflammatory cells compared with the OVA-treated mice. The levels of type 2 cytokines in the bronchoalveolar lavage fluid and expression of OVA-specific immunoglobulin E in the serum, which were elevated in the OVA group, were reduced in the KRG-treated groups. The pro-inflammatory factors, inducible nitric oxide synthase and nuclear factor kappa-light-chain-enhancer of activated B cells, were downregulated by the KRG administration in a dose-dependent manner. KRG effectively suppressed the inflammatory response by inhibiting ROS production. Our results suggest that KRG may have the potential to alleviate asthma.

Diallyl disulfide prevents 1,3-dichloro-2-propanol-induced hepatotoxicity through mitogen-activated protein kinases signaling.

We investigated whether diallyl disulfide (DADS) has protective effects against 1,3-dichloro-2-propanol (1,3-DCP)-induced hepatotoxicity and oxidative damage in rats and HepG2 cells. DADS was administered to rats once daily for 7 days at doses of 30 and 60 mg/kg/day. One hour after the final DADS treatment, the rats were administered 90 mg/kg 1,3-DCP to induce acute hepatotoxicity. DADS treatment significantly suppressed the increase in serum aminotransferase levels induced by 1,3-DCP administration, and reduced histopathological alterations in the liver. DADS treatment reduced 1-3-DCP-induced apoptotic changes in the liver, as revealed by terminal deoxynucleotidyl transferase dUTP nick end labeling staining and immunohistochemistry for caspase-3. DADS treatment competitively inhibited or reduced cytochrome p450 2E1 (CYP2E1) expression, which is involved in the metabolic activation of 1,3-DCP, and enhanced antioxidant properties. Furthermore, DADS treatment inhibited phosphorylation of mitogen-activated protein kinases (MAPKs) and apoptotic signaling. In in vitro experiments, MAPKs inhibitors reduced the expression of Bax/Bcl-2/Caspase 3 signaling, which effects were more significant in co-treated cells with DADS and MAPKs inhibitors. In conclusion, the protective effect of DADS against 1,3-DCP-induced hepatotoxicity may be related to blocking the metabolic activation of 1,3-DCP by suppressing CYP2E1 expression, inducing antioxidant enzyme activity, and reducing apoptotic activity by inhibiting phosphorylation of MAPKs.

Prophylactic Catechin-Rich Green Tea Extract Treatment Ameliorates Pathogenic Enterotoxic Escherichia coli-Induced Colitis.

In this study, we explored the potential beneficial effects of green tea extract (GTE) in a pathogenic Escherichia coli (F18:LT:STa:Stx2e)-induced colitis model. The GTE was standardized with catechin and epigallocatechin-3-gallate content using chromatography analysis. Ten consecutive days of GTE (500 and 1000 mg/kg) oral administration was followed by 3 days of a pathogenic E. coli challenge (1 × 109 CFU/mL). In vitro antibacterial analysis showed that GTE successfully inhibited the growth of pathogenic E. coli, demonstrating over a 3-fold reduction under time- and concentration-dependent conditions. The in vivo antibacterial effect of GTE was confirmed, with an inhibition rate of approximately 90% when compared to that of the E. coli alone group. GTE treatment improved pathogenic E. coli-induced intestinal injury with well-preserved epithelial linings and villi. In addition, the increased expression of annexin A1 in GTE-treated jejunum tissue was detected, which was accompanied by suppressed inflammation-related signal expression, including TNFA, COX-2, and iNOS. Moreover, proliferation-related signals such as PCNA, CD44, and Ki-67 were enhanced in the GTE group compared to those in the E. coli alone group. Taken together, these results indicate that GTE has an antibacterial activity against pathogenic E. coli and ameliorates pathogenic E. coli-induced intestinal damage by modulating inflammation and epithelial cell proliferation.

Identification of psychiatric disorder subtypes from functional connectivity patterns in resting-state electroencephalography.

The understanding and treatment of psychiatric disorders, which are known to be neurobiologically and clinically heterogeneous, could benefit from the data-driven identification of disease subtypes. Here, we report the identification of two clinically relevant subtypes of post-traumatic stress disorder (PTSD) and major depressive disorder (MDD) on the basis of robust and distinct functional connectivity patterns, prominently within the frontoparietal control network and the default mode network. We identified the disease subtypes by analysing, via unsupervised and supervised machine learning, the power-envelope-based connectivity of signals reconstructed from high-density resting-state electroencephalography in four datasets of patients with PTSD and MDD, and show that the subtypes are transferable across independent datasets recorded under different conditions. The subtype whose functional connectivity differed most from those of healthy controls was less responsive to psychotherapy treatment for PTSD and failed to respond to an antidepressant medication for MDD. By contrast, both subtypes responded equally well to two different forms of repetitive transcranial magnetic stimulation therapy for MDD. Our data-driven approach may constitute a generalizable solution for connectome-based diagnosis.

Clinical significance of anti-dense fine speckled 70 antibody in patients with fibromyalgia.

BACKGROUND/AIMS: Fibromyalgia (FM) is a common rheumatologic disease characterized by chronic widespread pain, along with various clinical manifestations including atypical autoimmune characteristics. Despite its high prevalence, there remain no approved laboratory tests to identify specific manifestations of FM, or to rule out FM from other rheumatic diseases. Anti-dense fine speckled 70 (anti-DFS70) antibodies were initially identified as a form of anti-nuclear antibodies in a patient with interstitial cystitis. Anti-DFS70 antibodies are found in ≤ 10% of healthy individuals, but have suggestive negative association with autoimmune diseases; however, the clinical significance of these autoantibodies in FM patients remains poorly understood. METHODS: We examined 39 patients with FM, along with 17 patients with systemic lupus erythematosus (SLE), and 19 healthy individuals (HI). Patients were compared based on physical measurements, disease duration, tender point counts, FM Impact Questionnaire (FIQ) scores, visual analog scale (VAS) for pain, somatic symptoms, and anti-DFS70 antibodies. RESULTS: Levels of anti-DFS70 antibodies were significantly higher in the FM and HI groups than in those with SLE. Both anti-DFS70 antibodies and VAS scores were positively correlated with FM. Within the FM group, patients with arthralgia had higher anti-DFS70 antibody values compared to those without arthralgia (p = 0.024); antibody levels were also higher in patients with sleep disturbances relative to those without sleep issues (p = 0.024). In contrast, there were no correlations between anti-DFS70 antibodies and age, body mass index, disease duration, tender point counts, FIQ, short-form health survey results, or other clinical manifestations. CONCLUSION: Anti-DFS70 antibodies may represent a useful biomarker for differentiating between FM and other autoimmune diseases. The levels of anti-DFS70 antibodies were also significantly higher among patients with arthralgia and sleep disturbances. Further investigations are necessary to evaluate the relationships between anti-DFS70 antibodies and other cytokines as a predictive marker for pain.