Tumor necrosis factor receptor-associated factor 3 (TRAF3) is an anti-inflammatory molecule that negatively regulates the non-canonical nuclear factor-κB pathway. Although TRAF3 haploinsufficiency (TRAF3 HI) can influence innate and adaptive immune cells, its effect on inflammatory bowel disease (IBD) development remains unclear. Here, we report the first case of severe early-onset IBD with a novel TRAF3 variant leading to HI, successfully treated with ustekinumab. A 6-year-old girl with a recurrent parotitis, otitis media, tonsilitis, and atopic dermatitis developed IBD involving the stomach, small intestine, and colon. At diagnosis, the immunoglobulin (Ig)G and IgA levels were relatively high, and lymphocyte subsets showed increased counts of plasmablasts, class-switch recombination B cells, and circulating T-follicular helper cells. Treatment with azathioprine and infliximab failed to maintain remission marked by several relapses accompanied by erythema nodosum and arthritis; however, ustekinumab, an anti-interleukin (IL)-12/23p40 antibody, led to long-term clinical remission, normalizing the Ig level and reducing abnormal lymphocyte counts. Whole-exome sequencing revealed a novel heterozygous mutation in TRAF3 [p.(Pro487Leufs*8)], resulting in TRAF3 under-expression. Our case may highlight the contribution of TRAF3 HI to the development of IBD and provide insights into IBD pathophysiology, suggesting the involvement of the IL-12/23-T-follicular helper cell pathway affected by genetic mutations.

Prostate cancer is one of the most common diseases in men worldwide. Surgery, radiation therapy, and hormonal therapy are effective treatments for early-stage prostate cancer. However, the development of castration-resistant prostate cancer has increased the mortality rate of prostate cancer. To develop novel drugs for castration-resistant prostate cancer, the molecular mechanisms of prostate cancer progression must be elucidated. Among the signaling pathways regulating prostate cancer development, recent studies have revealed the importance of noncanonical wingless-type MMTV integration site family (WNT) signaling pathways, mainly that involving WNT5A, in prostate cancer progression and metastasis; however, its role remains controversial. Moreover, chromatin remodelers such as the switch/sucrose nonfermentable (SWI/SNF) complex and chromodomain helicase DNA-binding proteins 1 also play important roles in prostate cancer progression through genome-wide gene expression changes. Here, we review the roles of noncanonical WNT signaling pathways, chromatin remodelers, and epigenetic enzymes in the development and progression of prostate cancer.
Male ; Humans ; Wnt Signaling Pathway ; Chromatin ; Prostatic Neoplasms, Castration-Resistant ; Chromatin Assembly and Disassembly

Chi-no-michi-sho involves neuropsychiatric and physical symptoms that appear with hormonal changes, such as those during pregnancy and menopause. Until now, there were many case reports, which were within 2 years from the start of treatment. We present a case of chi-no-michi-sho that was successfully treated with Kampo formulations for 7 years. A 43-­year-­old woman had complaints of candida eczema in the vulva, palpi­tations, and headache. Tokishakuyakusan and shakanzoto were then administered for kekkyo (blood defi­ciency), oketsu (blood stasis), and suidoku (fluid retention), and a topical antifungal agent was administered for candida eczema. The headache and palpitations were reduced. Subsequently, tokishigyakukagoshuyuto and keishibukuryogan were administered because of skin rash and deterioration of sensitivity to cold. However, various symptoms, such as weight loss amenorrhea due to self-­determination, eczema, feeling heavy in the head, and edema, remained. We prescribed tokishakuyakusan again in addition to Western medical treatment. Her menstruation then resumed ; her eczema, palpitations, and headache also improved. However, she developed hyperthyroidism. While paying attention to organic diseases such as thyroid dysfunction, prescription of tokishakuyakusan may be effective when chi-no-michi-sho is long­-lasting and there are blood deficiency and stasis with fluid retention.

The patch test is the most reliable method for diagnosing a metal allergy. However, interpretation of patch test results depends on the experience of the investigator and on the conditions of the individual patient. In the case of patch tests for metal salts, irritant reactions such as pustular or follicular reactions are quite common. Therefore, one must be careful not to interpret irritant reactions as allergic responses, and objective standards to evaluate erythema in patch tests need to be established.In the present study, we attempted to objectively evaluate patch test results for metal salts using an erythema index meter. We used the Erythema Index Difference (EID) (patch test site erythema index (EI) minus the mean EI of healthy skin outside the patch test area and at the unit tape site) rather than the EI itself in order to eliminate the effects of the patch test unit and individual differences. We measured the EID over time in patients with suspected metal allergies to various metals. Significant differences in EID were observed among ++ assessments, + assessments and irritant reactions based on International Contact Dermatitis Research Group (ICDRG) standards. In considering changes in EID over time, allergic and irritant reactions can be discriminated with high sensitivity (73.3%) and specificity (91.2%).These results suggest that the measurement of erythema over time with an erythema index meter is useful for the objective assessment of metal patch test reactions.