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Mixed neuroendocrine-nonneuroendocrine neoplasms (MiNENs) of the gastrointestinal tract, particularly gastric MiNENs are rare, and a gastric adenoma that occurs concomitant with a neuroendocrine carcinoma (and not gastric adenocarcinoma) is extremely rare. The clinicopathologic and pathogenetic features of MiNENs remain unclear, and treatment guidelines are currently unavailable. A 75-year-old man patient was referred to our hospital for management of a gastric adenoma. Endoscopy revealed an elevated mucosal lesion (10 mm×10 mm) at the greater curvature of the lower gastric body. The patient underwent endoscopic submucosal dissection for removal of the gastric neoplasm. Histopathological evaluation revealed mixed epithelial dysplasia, low and partly high grade and a neuroendocrine tumor (grade 1). Immunohistochemical analysis showed neoplastic cells with immunopositivity for CD56, synaptophysin, and INSM1, and Ki-67 showed 2.2%. Therefore, the patient was diagnosed with a low-grade gastric MiNEN. We present a rare case of gastric MiNENs (adenoma-neuroendocrine tumor) together with a literature review.
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Background@#This study aimed to evaluate the association between exposure to occupational hazards and the metabolic syndrome. A secondary objective was to analyze the additive and multiplicative effects of exposure to risk factors. @*Methods@#This retrospective cohort was based on 31,615 health examinees at the Pusan National University Yangsan Hospital in Republic of Korea from 2012–2021. Demographic and behavior-related risk factors were treated as confounding factors, whereas three physical factors, 19 organic solvents and aerosols, and 13 metals and dust were considered occupational risk factors. Time-dependent Cox regression analysis was used to calculate hazard ratios. @*Results@#The risk of metabolic syndrome was significantly higher in night shift workers (hazard ratio = 1.45: 95% confidence interval = 1.36–1.54) and workers who were exposed to noise (1.15:1.07–1.24). Exposure to some other risk factors was also significantly associated with a higher risk of metabolic syndrome. They were dimethylformamide, acetonitrile, trichloroethylene, xylene, styrene, toluene, dichloromethane, copper, antimony, lead, copper, iron, welding fume, and manganese. Among the 28 significant pairs, 19 exhibited both positive additive and multiplicative effects. @*Conclusions@#Exposure to single or combined occupational risk factors may increase the risk of developing metabolic syndrome. Working conditions should be monitored and improved to reduce exposure to occupational hazards and prevent the development of the metabolic syndrome.
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Purpose@#The aim of this study was to evaluate the diagnostic value of shear-wave elastography (SWE) combined with Doppler ultrasonography (US) in selecting equivocal breast fibroepithelial lesions (FELs) for follow-up without further excision. @*Methods@#A retrospective analysis was conducted of 88 patients with equivocal breast FELs (FELs with the possibility of both fibroadenoma [FA] and phyllodes tumor [PT]) diagnosed by core needle biopsy (CNB). For post-CNB treatment, surgical or vacuum-assisted excision was performed on 88 equivocal FELs, of which 56 were diagnosed as FAs and 32 as PTs on histopathology. Mean elasticity (Emean) and vascularity were determined using SWE and Doppler US. The diagnostic performances of B-mode US, SWE, and Doppler US were calculated to differentiate FAs and PTs in the excised equivocal FELs. @*Results@#In the excised equivocal FELs diagnosed by CNB, FAs showed significantly lower median Emean values (36.4 vs. 66.7 kPa, P=0.005) and more frequent low vascularity (0–1 vessel flow signal) (P60.9 kPa and high vascularity (≥2 vessel flows) showed a sensitivity and negative predictive value of 100%, as well as better performance in other diagnostic values than B-mode US alone (Breast Imaging Reporting and Data System ≥4A) (all P<0.05). @*Conclusion@#Equivocal breast FELs showing both low elasticity and low vascularity were not upgraded to PTs upon further excision. Therefore, the combination of SWE and color Doppler US mode might help select patients with equivocal FELs for whom further excision is unnecessary.
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Background@#Dietary Na+ or Na+/K+ ratio has been reported to be associated with bone mineral density (BMD). However, this remains unclear, and only a few studies have been reported on the Korean population. Therefore, this study aimed to determine the association between dietary Na+, K+, and Na+/K+ ratios and BMD in middle-aged Korean women. @*Methods@#This study used data from the Korea National Health and Nutrition Examination Survey 2008–2011. A total of 3,690 women aged >50 years were included. Study participants were classified into quartiles (lowest quartile Q1–highest quartile Q4) according to dietary Na+, K+, and Na+/K+ ratio, and we examined the association of these parameters with BMD. Total femur and lumbar spine BMD were measured using dual-energy X-ray absorptiometry. Multiple linear regression analyses were performed using IBM SPSS ver. 19.0. @*Results@#The mean age was 62 years, and a significant negative trend in the β-coefficient regarding dietary Na+ was only observed in the total femur BMD. However, the total femur and lumbar spine BMD decreased from Q1 to Q4 regarding the dietary Na+/K+ ratio (P-value for trend: 0.044 for total femur BMD and 0.002 for lumbar spine BMD). @*Conclusion@#A significant negative trend in the β-coefficient for both total femur and lumbar spine BMD was observed regarding the Na+/K+ ratio. Therefore, based on the results of this study, a higher dietary Na+/K+ ratio may be associated with a lower BMD.
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Acute hyperammonemic encephalopathy is generally associated with severe liver disease, manifesting with neuropsychiatric symptoms including confusion, lethargy, seizure, coma, and even death. Electroencephalogram (EEG) is a proven diagnostic, prognostic, and therapeutic tool in patients with acute and chronic encephalopathies. EEG changes in acute hyperammonemic encephalopathy are associated with background slowing in theta to delta ranges, accompanied by presence of triphasic waves. We reported a patient with acute hyperammonemic encephalopathy showing an unusual burst-suppression pattern, which was reversible with proper treatment.
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Background/Aims@#Lactase deficiency, which has many similarities with small intestinal bacterial overgrowth (SIBO), causes various gastrointestinal symptoms. We estimate the prevalence of SIBO in patients with intestinal symptoms from dairy products and investigate the association between lactase deficiency (LD) and SIBO. @*Methods@#This prospective study included patients with functional intestinal symptoms from dairy product indigestion. A questionnaire on gastrointestinal symptoms, a hydrogen (H 2 )-methane glucose breath test (GBT) for SIBO, and lactose intolerance quick test (LQT) for LD using upper gastrointestinal endoscopy were performed. @*Results@#A total of 88 patients, 29 (33.0%) with severe and 36 (40.9%) with mild LD were included. Sixteen patients (18.2%) were GBT positive. Patients with LQT negativity indicating severe LD showed a higher positivity to GBT or GBT (H 2 ) than the historic controls (27.6% vs 6.7%, P = 0.032). There was no difference in the items on the symptom questionnaire according to the presence of LD or SIBO, except for higher symptom scores for urgency in GBT-positive patients. There were more LQT-negative patients in the GBT (H 2 )-positive group than in the other groups (27.6% vs 10.2%, P = 0.036). Moreover, only GBT (H 2 )-positivity was significantly associated with a higher risk of LQT negativity in multivariate analysis (OR, 4.19; P = 0.029). @*Conclusions@#SIBO producing H 2is common in patients with severe LD suspected lactose intolerance. SIBO may be a new therapeutic target for managing intestinal symptoms in patients with lactose intolerance.
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Background@#A study on coronavirus disease 2019 (COVID-19) phobia among students revealed that fear of contracting COVID-19 was associated with commuting to school and spending time with others at school. Therefore, it is the need-of-the-hour for the Korean government to identify factors affecting COVID-19 phobia among university students and to consider these factors while framing the policy direction for the process of returning to normalcy in university education. Consequently, we aimed to identify the current state of COVID-19 phobia among Korean undergraduate and graduate students and the factors affecting COVID-19 phobia. @*Methods@#This cross-sectional survey was conducted to identify the factors affecting COVID-19 phobia among Korean undergraduate and graduate students. The survey collected 460 responses from April 5 to April 16, 2022. The questionnaire was developed based on the COVID-19 Phobia Scale (C19P-S). Multiple linear regression was performed on the C19P-S scores using five models with the following dependent variables: Model 1, total C19P-S score; Model 2, psychological subscale score; Model 3, psychosomatic subscale score; Model 4, social subscale score; and Model 5, economic subscale score. The fit of these five models was established, and a P-value of less than 0.05 (F test) was considered statistically significant. @*Results@#An analysis of the factors affecting the total C19P-S score led to the following findings: women significantly outscored men (difference: 4.826 points, P = 0.003); the group that favored the government’s COVID-19 mitigation policy scored significantly lower than those who did not favor it (difference: 3.161 points, P = 0.037); the group that avoided crowded places scored significantly higher than the group that did not avoid crowded places (difference: 7.200 points, P < 0.001); and those living with family/friends scored significantly higher than those in other living situations (difference: 4.606 points, P = 0.021). Those in favor of the COVID-19 mitigation policy had significantly lower psychological fear than those who were against it (difference: -1.686 points, P = 0.004). Psychological fear was also significantly higher for those who avoided crowded places compared to those who did not difference: 2.641 points, P < 0.001). Fear was significantly higher in people cohabitating than those living alone (difference: 1.543 points, P= 0.043). @*Conclusion@#The Korean government, in their pursuit of a policy that eases COVID-19-related restrictions, will also have to spare no efforts in providing correct information to prevent the escalation of COVID-19 phobia among people with a high fear of contracting the disease. This should be done through trustworthy information sources, such as the media, public agencies, and COVID-19 professionals.
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Background@#We evaluated the protective effects of melatonin against high-fat diet (HFD)-induced deterioration of bone microarchitecture using high-resolution peripheral quantitative computed tomography (HR-pQCT). @*Methods@#Four-week-old male C57BL/6 mice were divided into control (chow diet group), HFD, and HFD + melatonin-administered groups. Mice were sacrificed after 14 weeks, and the right femur was extracted. The microskeletal structure of the femur was analyzed using SkyScan1173 (version 1.6). A 3-dimensional image was reconstructed using the Nrecon (version 1.7.0.4) program. @*Results@#Bone volume (BV) was significantly increased in the HFD group compared with that in the normal diet group, and that of the melatonin group also increased significantly compared with BV of the normal diet group (p<0.05). Percent BV/total volume [TV] and bone surface/BV were significantly higher in both the HFD and melatonin groups than in the normal diet group (p<0.05), and the melatonin group had the highest BV/total volume (TV). BMD was lower in the HFD than in the normal diet group and was the highest in the melatonin group. @*Conclusions@#This study shows that melatonin inhibited the deterioration of microarchitecture induced by a HFD. A better understanding of the protective effect of melatonin on bone microarchitecture and mechanisms could provide fracture prevention for people who are obese.
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Background/Aims@#The prevalence of nonalcoholic fatty liver disease (NAFLD) has increased rapidly as a consequence of more sedentary lifestyles and a Westernized diet. Fracture is a major clinical problem in older people, but few large-scale cohort studies have evaluated the relationship between NAFLD and fracture. Therefore, we aimed to determine whether the fatty liver index (FLI), which represents the severity of NAFLD, can predict fracture risk. @*Methods@#We analyzed the relationship between the FLI and incident fracture using multivariate Cox proportional hazards models and data for 180,519 individuals who underwent National Health check-ups in the Republic of Korea between 2009 and 2014. @*Results@#A total of 2,720 participants (1.5%) were newly diagnosed with fracture during the study period (median 4.6 years). The participants were grouped according to FLI quartiles (Q1, 0 to <5.653; Q2, 5.653 to <15.245; Q3, 15.245 to <37.199; and Q4 ≥37.199). The cumulative fracture incidence was significantly higher in the highest FLI group than in the lowest FLI group (Q4, 986 [2.2%] and Q1, 323 [0.7%]; p<0.001). The adjusted hazard ratio indicated that the highest FLI group was independently associated with a higher incidence of fracture (hazard ratio for Q4 vs Q1, 2.956; 95% confidence interval, 2.606 to 3.351; p<0.001). FLI was significantly associated with a higher incidence of fracture, independent of the baseline characteristics of the participants. @*Conclusions@#Our data imply that the higher the FLI of a Korean patient is, the higher their risk of osteoporotic fracture, independent of key confounding factors.
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Sarcopenia, defined as a progressive loss of muscle mass and function, is typified by mitochondrial dysfunction and loss of mitochondrial resilience. Sarcopenia is associated not only with aging, but also with various metabolic diseases characterized by mitochondrial dyshomeostasis. Pyruvate dehydrogenase kinases (PDKs) are mitochondrial enzymes that inhibit the pyruvate dehydrogenase complex, which controls pyruvate entry into the tricarboxylic acid cycle and the subsequent adenosine triphosphate production required for normal cellular activities. PDK4 is upregulated in mitochondrial dysfunction-related metabolic diseases, especially pathologic muscle conditions associated with enhanced muscle proteolysis and aberrant myogenesis. Increases in PDK4 are associated with perturbation of mitochondria-associated membranes and mitochondrial quality control, which are emerging as a central mechanism in the pathogenesis of metabolic disease-associated muscle atrophy. Here, we review how mitochondrial dysfunction affects sarcopenia, focusing on the role of PDK4 in mitochondrial homeostasis. We discuss the molecular mechanisms underlying the effects of PDK4 on mitochondrial dysfunction in sarcopenia and show that targeting mitochondria could be a therapeutic target for treating sarcopenia.
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BACKGROUND/OBJECTIVES@#As peanuts germinate, the content of the components beneficial to health, such as resveratrol, increases within the peanut sprout. This study examined whether the ethanol extract of peanut sprout tea (PSTE) inhibits breast cancer growth and metastasis.MATERIALS/METHODS: After orthotopically injecting 4T1 cells into BALB/c mice to induce breast cancer, 0, 30, or 60 mg/kg body weight/day of PSTE was administered orally.Angiogenesis-related protein expression in the tumors and the degree of metastasis were analyzed. 4T1 and RAW 264.7 cells were co-cultured, and reverse transcription polymerase chain reaction was performed to measure the crosstalk between breast cancer cells and macrophages. @*RESULTS@#PSTE reduced tumor growth and lung metastasis. In particular, PSTE decreased matrix metalloproteinase-9, platelet endothelial cell adhesion molecule-1, vascular endothelial growth factor-A, F4/80, CD11c, macrophage mannose receptor, macrophage colony-stimulating factor, and monocyte chemoattractant protein 1 expression in the tumors. Moreover, PSTE prevented 4T1 cell migration, invasion, and macrophage activity in RAW 264.7 cells. PSTE inhibited the crosstalk between 4T1 cells and RAW 264.7 cells and promoted the macrophage M1 subtype while inhibiting the M2 subtype. @*CONCLUSIONS@#These results suggest that PSTE blocks breast cancer growth and metastasis to the lungs. This may be because the PSTE treatment inhibits the crosstalk between mammary cancer cells and macrophages and inhibits the differentiation of macrophages into the M2 subtype.
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BACKGROUND/OBJECTIVES@#The skin is the outermost organ of the human body and plays a protective role against external environmental damages, such as sunlight and pollution, which affect anti-oxidant defenses and skin inflammation, resulting in erythema or skin reddening, immunosuppression, and epidermal DNA damage.MATERIALS/METHODS: The present study aimed to investigate the potential protective effects of red orange complex H extract (ROC) against ultraviolet (UV)-induced skin photoaging in Skh:HR-2 mice. ROC was orally administered at doses of 20, 40, and 80 mg/ kg/day for 13 weeks, along with UV irradiation of the mice for 10 weeks. @*RESULTS@#ROC improved UV-induced skin barrier parameters, including erythema, melanin production, transepidermal water loss, elasticity, and wrinkle formation. Notably, ROC inhibited the mRNA expression of pro-inflammatory cytokines (interleukin 6 and tumor necrosis factor α) and melanogenesis. In addition, ROC recovered the UV-induced decrease in the hyaluronic acid and collagen levels by enhancing genes expression. Furthermore, ROC significantly downregulated the protein and mRNA expression of matrix metalloproteinases responsible for collagen degradation. These protective effects of ROC against photoaging are associated with the suppression of UV-induced phosphorylation of c-Jun NH2-terminal kinase and activator protein 1 activation. @*CONCLUSIONS@#Altogether, our findings suggest that the oral administration of ROC exerts potential protective activities against photoaging in UV-irradiated hairless mice.
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In this study, we investigated the efficacy of Celtis choseniana Nakai (C. choseniana) as complementary herbal medicine to ameliorate androgenic alopecia (AGA). The effects of C. choseniana on AGA were evaluated using testosterone propionate-induced AGA mouse model and dihydrotestosterone-treated human hair follicle dermal papilla cells. In vivo, C. choseniana treatment deactivated androgen signaling by reducing the concentration of serum dihydrotestosterone level and expressions of 5α-reductase 2 and androgen receptor. Next, C. choseniana treatment increased the hair regrowth rate. Histological studies demonstrated that C. choseniana induced the anagen phase in testosterone propionate-induced AGA mouse model. Cellular proliferation was promoted by C. choseniana treatment via increasing the expression of proliferation factors, such as proliferating cell nuclear antigen and cyclin D1. Furthermore, C. choseniana treatment increased the expression of proteins related to the Wnt/β-catenin signaling pathway. In addition, dickkopf-1, a Wnt inhibitor, was downregulated with C. choseniana treatment. Likewise, C. choseniana treatment promoted cellular proliferation in vitro. This study demonstrated the inhibitory effect of C. choseniana on androgen-induced AGA. Moreover, C. choseniana induced activation of Wnt/β-catenin signaling, resulting in prolonged anagen and cellular proliferation. Therefore, we suggest that C. choseniana can be used as a therapeutic agent to alleviate AGA.
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Background@#To date, various genotypes of infectious bronchitis virus (IBV) have cocirculated and in Korea, GI-15 and GI-19 lineages were prevailing. The spike protein, particularly S1 subunit, is responsible for receptor binding, contains hypervariable regions and is also responsible for the emerging of novel variants. @*Objective@#This study aims to investigate the putative major amino acid substitutions for the variants in GI-19. @*Methods@#The S1 sequence data of IBV isolated from 1986 to 2021 in Korea (n = 188) were analyzed. Sequence alignments were carried out using Multiple alignment using Fast Fourier Transform of Geneious prime. The phylogenetic tree was generated using MEGA-11 (ver.11.0.10) and Bayesian analysis was performed by BEAST v1.10.4. Selective pressure was analyzed via online server Datamonkey. Highlights and visualization of putative critical amino acid were conducted by using PyMol software (version 2.3). @*Results@#Most (93.5%) belonged to the GI-19 lineage in Korea, and the GI-19 lineage was further divided into seven subgroups: KM91-like (Clade A and B), K40/09-like, QX-like (I-IV).Positive selection was identified at nine and six residues in S1 for KM91-like and QX-like IBVs, respectively. In addition, several positive selection sites of S1-NTD were indicated to have mutations at common locations even when new clades were generated. They were all located on the lateral surface of the quaternary structure of the S1 subunits in close proximity to the receptor-binding motif (RBM), putative RBM motif and neutralizing antigenic sites in S1. @*Conclusions@#Our results suggest RBM surrounding sites in the S1 subunit of IBV are highly susceptible to mutation by selective pressure during evolution.
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Purpose@#The aim of this study was to investigate the anti-osteoarthritic effect of the ethanol extract of Boswellia serrata gum resin (FJH-UBS) enriched with keto-β-boswellic acid and 3-O-acetyl-11-keto-β-boswellic acid compared to the conventional Boswellia serrata extract by adding the process of removing oil with hexane, in the monosodium iodoacetate (MIA)-induced osteoarthritis rat model. @*Methods@#Sprague-Dawley (SD) rats were orally administered 0, 40, or 80 mg of FJH-UBS/kg body weight (BW)/day for 5 weeks and injected with MIA intra-articularly into right knee joints on day 15 to induce osteoarthritis. Changes in the knee joint microarchitecture, cartilage degradation, the expression of inflammatory mediators, cytokines, and matrix metalloproteinases (MMPs) in serum and synovia were observed. @*Results@#Oral administration of FJH-UBS (80 mg/kg BW/day) reduced MIA-induced knee swelling and cartilage degradation and increased the expression of type II collagen and aggrecan in articular cartilage. Furthermore, FJH-UBS administration reduced MIA-induced increases in the serum levels of prostaglandin E2, leukotriene B4, interleukin (IL)-1β, IL-6, and MMP-13, and MIA-induced increases in the mRNA expressions of inducible nitric oxide synthase, cyclooxygenase-2, 5-lipoxygenase, IL-1β, IL-6, TNF-α, MMP-2, MMP-9, and MMP-13 in the synovia of knee joints. @*Conclusion@#These results indicate that FJH-UBS exerts its anti-osteoarthritic effects by suppressing the expressions of inflammatory cytokines and MMPs and, thus, cartilage degradation. Furthermore, they suggest that FJH-UBS has potential use as a functional food that improves joint and cartilage health.
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The CYP11A1 gene encodes for the cholesterol side-chain cleavage enzyme (P450scc), which initiates steroid hormone biosynthesis. Defective P450scc activity results in severe glucocorticoid and mineralocorticoid deficiencies. We describe a case of P450scc deficiency due to a novel homozygous CYP11A1 variant inherited from the mother with a possibility of uniparental disomy (UPD). The patient was a female, had no family history of endocrine disease, and showed adrenal insufficiency at 13 days of age. Hormonal analysis with an adrenocorticotropic hormone stimulation test showed both glucocorticoid and mineralocorticoid deficiencies, presumed to be a defect of the early stage of steroidogenesis. Exome sequencing reported a novel homozygous frameshift variant of CYP11A1 (c.284_285del, p.Asn95Serfs*10), which was inherited from the mother.Additionally, homozygosity in 15q22.31q26.2, which included CYP11A1, was identified using a chromosomal microarray. It was suggested that the possibility of maternal UPD was involved as the cause of a P450scc deficiency by unmasking the maternally derived affected allele. To our understanding, P450scc deficiency associated with UPD encompassing CYP11A1 had not been reported in Korea before. Genetic analysis can help diagnose rare causes of primary adrenal insufficiency, including P450scc deficiency.
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Objectives@#Intraoperative navigation reduces the risk of major complications and increases the likelihood of optimal surgical outcomes. This paper presents an augmented reality (AR)-based simulation technique for ventriculostomy that visualizes brain deformations caused by the movements of a surgical instrument in a three-dimensional brain model. This is achieved by utilizing a position-based dynamics (PBD) physical deformation method on a preoperative brain image. @*Methods@#An infrared camera-based AR surgical environment aligns the real-world space with a virtual space and tracks the surgical instruments. For a realistic representation and reduced simulation computation load, a hybrid geometric model is employed, which combines a high-resolution mesh model and a multiresolution tetrahedron model. Collision handling is executed when a collision between the brain and surgical instrument is detected. Constraints are used to preserve the properties of the soft body and ensure stable deformation. @*Results@#The experiment was conducted once in a phantom environment and once in an actual surgical environment. The tasks of inserting the surgical instrument into the ventricle using only the navigation information presented through the smart glasses and verifying the drainage of cerebrospinal fluid were evaluated. These tasks were successfully completed, as indicated by the drainage, and the deformation simulation speed averaged 18.78 fps. @*Conclusions@#This experiment confirmed that the AR-based method for external ventricular drain surgery was beneficial to clinicians.
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Background/Aims@#Dual priming oligonucleotide-based multiplex polymerase chain reaction (DPO-PCR) has recently been used for both the detection of Helicobacter pylori and the identification of H. pylori 23S ribosomal RNA point mutations that cause clarithromycin resistance.The aim of this study was to investigate the duration of effective standard triple therapy in a clarithromycin susceptible group and of bismuth-based quadruple therapy in a resistant group based on DPO-PCR. @*Methods@#We retrospectively analyzed the electronic medical records of 184 patients who, between September 2019 and December 2020, received eradication therapy following detection of H. pylori, and the subsequent identification of the clarithromycin susceptibility of their H. pylori using DPO-PCR. Patients were treated with 7- or 14-day standard triple therapy in the clarithromycin susceptible group, whereas 7- or 14-day bismuth-based quadruple therapy in the clarithromycin resistance group. @*Results@#In the clarithromycin susceptible group, per-protocol analyses showed eradication rates of 87.5% (42/48; 95% confidence interval [CI], 77.1% to 95.8%) for 7-day therapy and 87.2% (41/47; 95% CI, 78.7% to 95.7%) for 14-day therapy (p=0.969). The eradication rates in the clarithromycin resistance group were 91.4% (32/35; 95% CI, 80.0% to 100.0%) for 7-day therapy and 90.3% (28/31; 95% CI, 77.4% to 100.0%) for 14-day therapy (p=0.876). There was no significant difference in the eradication rates, patient compliance, or rate of adverse events between the 7-and 14-day therapies for both groups. @*Conclusions@#Compared to the 14-day therapy, 7-day eradication therapy is sufficient after DPO-PCR-based clarithromycin susceptibility testing.
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Mental health is influenced by the gut-brain axis; for example, gut dysbiosis has been observed in patients with major depressive disorder (MDD).Gut microbial changes by fecal microbiota transplantation or probiotics treatment reportedly modulates depressive symptoms. However, it remains unclear how gut dysbiosis contributes to mental dysfunction, and how correction of the gut microbiota alleviates neuropsychiatric disorders. Our previous study showed that chronic consumption of Lactobacillus reuteri ATG-F4 (F4) induced neurometabolic alterations in healthy mice. Here, we investigated whether F4 exerted therapeutic effects on depressive-like behavior by influencing the central nervous system. Using chronic unpredictable stress (CUS) to induce anhedonia, a key symptom of MDD, we found that chronic F4 consumption alleviated CUS-induced anhedonic behaviors, accompanied by biochemical changes in the gut, serum, and brain. Serum and brain metabolite concentrations involved in tryptophan metabolism were regulated by CUS and F4. F4 consumption reduced the elevated levels of serotonin (5-HT) in the brain observed in the CUS group. Additionally, the increased expression of Htr1a, a subtype of the 5-HT receptor, in the medial prefrontal cortex (mPFC) of stressed mice was restored to levels observed in stress-naïve mice following F4 supplementation. We further demonstrated the role of Htr1a using AAV-shRNA to downregulate Htr1a in the mPFC of CUS mice, effectively reversing CUS-induced anhedonic behavior. Together, our findings suggest F4 as a potential therapeutic approach for relieving some depressive symptoms and highlight the involvement of the tryptophan metabolism in mitigating CUS-induced depressive-like behaviors through the action of this bacterium.
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Background@#CycloZ, a combination of cyclo-His-Pro and zinc, has anti-diabetic activity. However, its exact mode of action remains to be elucidated. @*Methods@#KK-Ay mice, a type 2 diabetes mellitus (T2DM) model, were administered CycloZ either as a preventive intervention, or as a therapy. Glycemic control was evaluated using the oral glucose tolerance test (OGTT), and glycosylated hemoglobin (HbA1c) levels. Liver and visceral adipose tissues (VATs) were used for histological evaluation, gene expression analysis, and protein expression analysis. @*Results@#CycloZ administration improved glycemic control in KK-Ay mice in both prophylactic and therapeutic studies. Lysine acetylation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha, liver kinase B1, and nuclear factor-κB p65 was decreased in the liver and VATs in CycloZ-treated mice. In addition, CycloZ treatment improved mitochondrial function, lipid oxidation, and inflammation in the liver and VATs of mice. CycloZ treatment also increased the level of β-nicotinamide adenine dinucleotide (NAD+), which affected the activity of deacetylases, such as sirtuin 1 (Sirt1). @*Conclusion@#Our findings suggest that the beneficial effects of CycloZ on diabetes and obesity occur through increased NAD+ synthesis, which modulates Sirt1 deacetylase activity in the liver and VATs. Given that the mode of action of an NAD+ booster or Sirt1 deacetylase activator is different from that of traditional T2DM drugs, CycloZ would be considered a novel therapeutic option for the treatment of T2DM.