Lactobacillus reuteri ATG-F4 Alleviates Chronic Stress-induced Anhedonia by Modulating the Prefrontal Serotonergic System

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.

Mental Disorders Linked to Crosstalk between The Gut Microbiome and The Brain

Often called the second brain, the gut communicates extensively with the brain and vice versa. The conversation between these two organs affects a variety of physiological mechanisms that are associated with our mental health. Over the past decade, a growing body of evidence has suggested that the gut microbiome builds a unique ecosystem inside the gastrointestinal tract to maintain the homeostasis and that compositional changes in the gut microbiome are highly correlated with several mental disorders. There are ongoing efforts to treat or prevent mental disorders by regulating the gut microbiome using probiotics. These attempts are based on the seminal findings that probiotics can control the gut microbiome and affect mental conditions. However, some issues have yet to be conclusively addressed, especially the causality between the gut microbiome and mental disorders. In this review, we focus on the mechanisms by which the gut microbiome affects mental health and diseases. Furthermore, we discuss the potential use of probiotics as therapeutic agents for psychiatric disorders.

Mental Disorders Linked to Crosstalk between The Gut Microbiome and The Brain

Often called the second brain, the gut communicates extensively with the brain and vice versa. The conversation between these two organs affects a variety of physiological mechanisms that are associated with our mental health. Over the past decade, a growing body of evidence has suggested that the gut microbiome builds a unique ecosystem inside the gastrointestinal tract to maintain the homeostasis and that compositional changes in the gut microbiome are highly correlated with several mental disorders. There are ongoing efforts to treat or prevent mental disorders by regulating the gut microbiome using probiotics. These attempts are based on the seminal findings that probiotics can control the gut microbiome and affect mental conditions. However, some issues have yet to be conclusively addressed, especially the causality between the gut microbiome and mental disorders. In this review, we focus on the mechanisms by which the gut microbiome affects mental health and diseases. Furthermore, we discuss the potential use of probiotics as therapeutic agents for psychiatric disorders.

Moxibustion for managing type 2 diabetes mellitus: a systematic review / 中国结合医学杂志

<p><b>OBJECTIVE</b>Moxibustion is currently used for treating diabetes mellitus (DM) as a non-drug intervention in East Asian countries. This systematic review aims to evaluate the effectiveness of moxibustion for managing the symptoms of type 2 DM patients.</p><p><b>METHODS</b>We searched MEDLINE, AMED, EMBASE, CINAHL, The Cochrane Library, six Korean databases, and four Chinese databases. Risk of bias was used for evaluating the quality of the included studies.</p><p><b>RESULTS</b>A total of 5 studies met the inclusion criteria for this review. All of the included studies had high risks of bias. One randomized clinical trial (RCT) compared the effectiveness of one-time moxibustion use with oral administration of glibenclimide and showed the significant effects of moxibustion on glycemic control. Another RCT tested the effectiveness of moxibustion plus conventional treatment, and the moxibustion group reported significant improvement in fasting and postprandial blood glucose levels compared with the conventional treatment group. Two RCTs compared the effectiveness of moxibustion versus acupuncture or moxibustion plus acupuncture, and the combined treatment showed the most favorable effects on the control of blood glucose, urine glucose, and glycocylated hemoglobin A(1c) (HbA(1c)). One uncontrolled observational study showed favorable effects of moxibustion on the response rate.</p><p><b>CONCLUSIONS</b>It is difficult to conclude that moxibustion is an effective intervention for the control of type 2 DM due to the scarcity of trials and the low methodological quality of included studies. Further rigorous RCTs may be necessary to evaluate the effectiveness of moxibustion for type 2 DM.</p>

Loss of Expression of the PTEN Gene Product in the Infiltrating Ductal Carcinoma of the Breast and Its Relationship with Clinicopathologic Factors / 한국유방암학회지

PURPOSE: PTEN is a novel tumor suppressor gene located on chromosomal band 10q23.3. The detection of PTEN mutations in Cowden disease and in breast carcinoma cell lines suggests that PTEN may be involved in mammary carcinogenesis. Among several series of breast carcinomas, the frequency of loss of flanking markers around PTEN is approximately 30 to 40% and the somatic intragenic PTEN mutation frequency is less than 5%. METHODS: The expression of PTEN was stuided immunohistochemically studied in 41 invasive ductal carcinomas of the breast. We examined the correlation between PTEN expression and clinicopathologic factors such as age, tumor size, lymph node metastasis, histologic grade, nuclear grade, stage, as well as estrogen and progesteron receptors. RESULTS: Among the 41 infiltrating ductal carcinomas, studied 7 (17.1%) were immunohistochemically negative, and 19 (46.3%) demonstrated reduced expression. Among the clinicopathologic factors, tumor size, lymph node metastasis, high stage, and negative progesteron receptor displayed a significant relationship with the decrease of PTEN expression, however age, nuclear grade, and estrogen receptor had less of a relationship with PTEN expression. CONCLUSION: These results suggest that PTEN does play some role as a prognostic factor for carcinogenesis, but this hypothesis requires further study.

Loss of Expression of the PTEN Gene Product in the Infiltrating Ductal Carcinoma of the Breast and Its Relationship with Clinicopathologic Factors

PURPOSE: PTEN is a novel tumor suppressor gene located on chromosomal band 10q23.3. The detection of PTEN mutations in Cowden disease and in breast carcinoma cell lines suggests that PTEN may be involved in mammary carcinogenesis. Among several series of breast carcinomas, the frequency of loss of flanking markers around PTEN is approximately 30 to 40% and the somatic intragenic PTEN mutation frequency is less than 5%. METHODS: The expression of PTEN was stuided immunohistochemically studied in 41 invasive ductal carcinomas of the breast. We examined the correlation between PTEN expression and clinicopathologic factors such as age, tumor size, lymph node metastasis, histologic grade, nuclear grade, stage, as well as estrogen and progesteron receptors. RESULTS: Among the 41 infiltrating ductal carcinomas, studied 7 (17.1%) were immunohistochemically negative, and 19 (46.3%) demonstrated reduced expression. Among the clinicopathologic factors, tumor size, lymph node metastasis, high stage, and negative progesteron receptor displayed a significant relationship with the decrease of PTEN expression, however age, nuclear grade, and estrogen receptor had less of a relationship with PTEN expression. CONCLUSION: These results suggest that PTEN does play some role as a prognostic factor for carcinogenesis, but this hypothesis requires further study.

Clinical Analysis of Primary Gallbladder Carcinoma to Improve Early Diagnosis

PURPOSE: The prognosis for primary gallbladder cancer is very poor. Because of the lack of specific symptoms, late diagnosis, advanced stage, and ineffective treatment are typical. The purpose of the present study was to investigate the early diagnostic factors that improve the survival rate, by comparing a preoperatively diagnosed group with a postoperatively diagnosed group. METHODS: This study was a clinical analysis of our surgical experience with primary gallbladder carcinomas during the 6 years from 1992 to 1997 at Chung-Ang University in Korea. RESULTS: The incidence of gallbladder carcinomas was 0.6% of the 6132 biliary-tract operations performed during the 6 years (suspected group: unsuspected group=15:23). The sex ratio of males to females was 1 to 2.46 with female predominance. Primary GB cancer was seen most commonly in patients in their 50s and 60s, and this group accounted for 68.4% of the entire group and had a median age of 65 years. The most common clinical manifestation was right upper abdominal pain in 27 cases (71.1%). The duration of the illness in preoperatively suspected patients was much shorter than that for intraoperatively or only pathologically diagnosed patients (p=0.046) As for diagnostic methods, ultrasound and abdominal CT scans were performed, and the preoperative diagnostic accuracies were 31.6% and 69.3%, respectively. The patients were grouped according to the staging system of Nevin et al. The five stages were classified as follows: stage I (suspected group-0 cases; unsuspected group-2 cases), stage II (1 case; 5 cases), stage III (1 case; 2 cases), stage IV (7 cases; 9 cases), and stage V (6 cases; 5 cases). Adenocarcinoma was the most common type of gallbladder cancer (32 cases: suspected group-10 cases; unsuspected group-22 cases), followed by squamoadenocarcinoma (3 cases: 2 cases/1 case), neurogenic carcinoma (1 case: 1 case/0 cases), histiocytoma (1 case: 1 case/0 cases), and papillary carcinoma (1 case: 1 case/0 cases). The total cumulative 1-year, 2-year, and 3-year survival rates were 67.7%, 37.6%, and 12.1%, respectively (suspected: 46.2%, 15.4%, and 0%; unsuspected: 71.4%, 52.9%, and 23.2%). The cumulative survival rates for patients in the unsuspected group were higher than those for patients in the suspected group (p=0.008). CONCLUSION: The survival rate of the preoperatively unsuspected group was better than that of the suspected group. The survival improvement depended the invasion by the gallbladder carcinoma. We suggest that the survival rate should be improved by early detection of the gallbladder carcinoma and on extended operation. Conclusively, further evaluation of patients with etiologic factors should be done, more specific exams (CT or MRI) should be evaluated, and an acceptable operation should be done.

Clinical Analysis of Primary Gallbladder Carcinoma to Improve Early Diagnosis

PURPOSE: The prognosis for primary gallbladder cancer is very poor. Because of the lack of specific symptoms, late diagnosis, advanced stage, and ineffective treatment are typical. The purpose of the present study was to investigate the early diagnostic factors that improve the survival rate, by comparing a preoperatively diagnosed group with a postoperatively diagnosed group. METHODS: This study was a clinical analysis of our surgical experience with primary gallbladder carcinomas during the 6 years from 1992 to 1997 at Chung-Ang University in Korea. RESULTS: The incidence of gallbladder carcinomas was 0.6% of the 6132 biliary-tract operations performed during the 6 years (suspected group: unsuspected group=15:23). The sex ratio of males to females was 1 to 2.46 with female predominance. Primary GB cancer was seen most commonly in patients in their 50s and 60s, and this group accounted for 68.4% of the entire group and had a median age of 65 years. The most common clinical manifestation was right upper abdominal pain in 27 cases (71.1%). The duration of the illness in preoperatively suspected patients was much shorter than that for intraoperatively or only pathologically diagnosed patients (p=0.046) As for diagnostic methods, ultrasound and abdominal CT scans were performed, and the preoperative diagnostic accuracies were 31.6% and 69.3%, respectively. The patients were grouped according to the staging system of Nevin et al. The five stages were classified as follows: stage I (suspected group-0 cases; unsuspected group-2 cases), stage II (1 case; 5 cases), stage III (1 case; 2 cases), stage IV (7 cases; 9 cases), and stage V (6 cases; 5 cases). Adenocarcinoma was the most common type of gallbladder cancer (32 cases: suspected group-10 cases; unsuspected group-22 cases), followed by squamoadenocarcinoma (3 cases: 2 cases/1 case), neurogenic carcinoma (1 case: 1 case/0 cases), histiocytoma (1 case: 1 case/0 cases), and papillary carcinoma (1 case: 1 case/0 cases). The total cumulative 1-year, 2-year, and 3-year survival rates were 67.7%, 37.6%, and 12.1%, respectively (suspected: 46.2%, 15.4%, and 0%; unsuspected: 71.4%, 52.9%, and 23.2%). The cumulative survival rates for patients in the unsuspected group were higher than those for patients in the suspected group (p=0.008). CONCLUSION: The survival rate of the preoperatively unsuspected group was better than that of the suspected group. The survival improvement depended the invasion by the gallbladder carcinoma. We suggest that the survival rate should be improved by early detection of the gallbladder carcinoma and on extended operation. Conclusively, further evaluation of patients with etiologic factors should be done, more specific exams (CT or MRI) should be evaluated, and an acceptable operation should be done.