In bladder cancer, urothelial carcinoma is the most common histologic subtype, accounting for more than 90% of cases. Pathogenic effects due to the dysbiosis of gut microbiota are localized not only in the colon, but also in regulating bladder cancer distally. Butyrate, a short-chain fatty acid produced by gut microbial metabolism, is mainly studied in colon diseases. Therefore, the resolution of the anti-cancer effects of butyrate-producing microbes on bladder urothelial cells and knowledge of the butyrate-responsive molecules must have clinical significance. Here, we demonstrate a correlation between urothelial cancer of the bladder and Butyricicoccus pullicaecorum. This butyrate-producing microbe or their metabolite, butyrate, mediated anti-cancer effects on bladder urothelial cells by regulating cell cycle, cell growth, apoptosis, and gene expression. For example, a tumor suppressor against urothelial cancer of the bladder, bladder cancer-associated protein, was induced in butyrate-treated HT1376 cells, a human urinary bladder cancer cell line. In conclusion, urothelial cancer of the bladder is a significant health problem. To improve the health of bladder urothelial cells, supplementation of B. pullicaecorum may be necessary and can further regulate butyrate-responsive molecular signatures.

Magnolol, which is a CYP3A substrate, is a well-known agent that can facilitate neuroprotection and reduce ischemic brain damage. However, a well-controlled release formulation is needed for the effective delivery of magnolol due to its poor water solubility. In this study, we have developed a formulation for a CYP3A-excipient microemulsion, which can be administrated intraperitoneally to increase the solubility and bioavailability of magnolol and increase its neuroprotective effect against ischemic brain injury. The results showed a significant improvement in the area under the plotted curve of drug concentration versus time curve (AUC0–t) and mean residence time (MRT) of magnolol in microemulsion compared to when it was dissolved in dimethyl sulfoxide (DMSO). Both magnolol in DMSO and microemulsion, administrated after the onset of ischemia, showed a reduced visual brain infarct size. As such, this demonstrates a therapeutic effect on ischemic brain injury caused by occlusion, however it is important to note that a pharmacological effect cannot be concluded by this study. Ultimately, our study suggests that the excipient inhibitor-based microemulsion formulation could be a promising concept for the substrate drugs of CYP3A.

Little is known about genes that induce stem cells differentiation into astrocytes. We previously described that heat shock protein 27 (HSP27) downregulation is directly related to neural differentiation under chemical induction in placenta-derived multipotent stem cells (PDMCs). Using this neural differentiation cell model, we cross-compared transcriptomic and proteomic data and selected 26 candidate genes with the same expression trends in both omics analyses. Those genes were further compared with a transcriptomic database derived from Alzheimer’s disease (AD). Eighteen out of 26 candidates showed opposite expression trends between our data and the AD database. The mRNA and protein expression levels of those candidates showed downregulation of HSP27, S100 calcium-binding protein A16 (S100A16) and two other genes in our neural differentiation cell model. Silencing these four genes with various combinations showed that co-silencing HSP27 and S100A16 has stronger effects than other combinations for astrocyte differentiation. The induced astrocyte showed typical astrocytic star-shape and developed with ramified, stringy and filamentous processes as well as differentiated endfoot structures. Also, some of them connected with each other and formed continuous network. Immunofluorescence quantification of various neural markers indicated that HSP27 and S100A16 downregulation mainly drive PDMCs differentiation into astrocytes. Immunofluorescence and confocal microscopic images showed the classical star-like shape morphology and co-expression of crucial astrocyte markers in induced astrocytes, while electrophysiology and Ca²⁺ influx examination further confirmed their functional characteristics. In conclusion, co-silencing of S100A16 and HSP27 without chemical induction leads to PDMCs differentiation into functional astrocytes. Graphical abstract

Background: Neuroplasticity induced by neonatal inflammation is the consequence of a combination of activity-dependent changes in neurons. We investigated neuronal sensitivity to a noxious stimulus in a rat model of neonatal hind-paw peripheral inflammation and assessed changes in pain behaviour at the physiological and molecular levels after peripheral reinflammation in adulthood.Results: A decrease in paw withdrawal latency (PWL) after a heat stimulus was documented in rats that received inflammatory injections in their left hind paws on postnatal day one (P1) and a reinflammation stimulus at postnatal 6-8 weeks of age, compared with normal rats. An increase in the expression of the prodynorphin (proDYN) gene was noted after reinflammation in the spinal cord ipsilateral to the afferents of the neonatally treated hind paw. The involvement of the activation of extracellular signal-regulated kinases (ERK) in peripheral inflammatory pain hypersensitivity was evidenced evident by the increase in phospho-ERK (pERK) activity after reinflammation.Conclusions: Our results indicate that peripheral inflammation in neonates can permanently alter the pain processing pathway during the subsequent sensory stimulation of the region. Elucidation of the mechanism underlying the developing pain circuitry will provide new insights into the understanding of the early pain behaviours and the subsequent adaptation to pain.

Objective: To understand the risk of developing a poor prognosis in adulthood after violent injury in Taiwan. Methods: This study used the data of outpatients, from emergency departments, and from hospitalization of 2 million people under National Health Insurance from 2000 to 2015. The ICD-9 diagnostic code N-code was defined as the case of this study and was 995.8 (abused adult) or E-code was E960-E969 (homicide and intentional injury by others) The first violent injury of 18–64-year-old adults (the study group) was analyzed. Patients who had not suffered violent abuse were the control group. The groups were matched in a 1:4 ratio, and the paired variables were gender, age ±1 year, Charlson Comorbidity index (CCI) before exposure, and year of medical treatment. SAS 9.4 statistical software was used, and the Cox regression method was used for data analysis. Results: During the 15-year period, a total of 8726 people suffered from violence (34,904 controls). The incidences of common poor prognoses among the victims of violence were sleep disorder, anxiety, and depression, in 33.9%, 21.6%, and 13.2% of people, respectively. The risk (Adults, Overall) of developing Post-Traumatic Stress Disorder (PTSD), bipolar disorder, and manic disorder after being violently injured (average 9 years) was 34.86, 4.4, and 4.1 times higher than those who had not suffered violence (all p values < 0.01). The risk (Adults, Males) of developing PTSD, bipolar disorder, and manic disorder after being violently injured (average 9 years) was 30.0, 3.81, and 2.85 times higher, respectively, than those who had not suffered violence (all p values < 0.01). The risk (Adults, Females) of developing PTSD, manic disorder, and bipolar disorder after being violently injured (average 9 years) was 36.8, 6.71, and 5.65 times higher, respectively, than of those who had not suffered violence (all p values < 0.01). Conclusion: The risks of poor prognosis are higher in adults who have suffered violent abuse than in those who have not. Therefore, police, social workers, and medical personnel should pay attention to the mental state of victims of violence. They should aim to support prompt treatment, to avoid PTSD, bipolar disorder, manic disorder, etc.