Downregulation of SMAD4 protects HaCaT cells against UVB-induced damage and oxidative stress through the activation of EMT.

As a member of the SMAD family, SMAD4 plays a crucial role in several cellular biological processes. However, its function in UVB radiation-induced keratinocyte damage is not yet clarified. Our study aims to provide mechanistic insight for the development of future UVB protective therapies and therapeutics involving SMAD4. HaCaT cells were treated with UVB, and the dose dependence and time dependence of UVB were measured. The cell function of UVB-treated HaCaT cells and the activity of epithelial-mesenchymal transition (EMT) after overexpression or silencing of SMAD4 was observed by flow cytometry, quantitative reverse transcription PCR (qRT-PCR) and Western Blots (WB). We found that a significant decrease in SMAD4 was observed in HaCaT cells induced by UVB. Our data confirm SMAD4 as a direct downstream target of miR-664. The down-regulation of SMAD4 preserved the viability of the UVB-treated HaCaT cells by inhibiting autophagy or apoptosis. Furthermore, the silencing of SMAD4 activated the EMT process in UVB-treated HaCaT cells. Down-regulation of SMAD4 plays a protective role in UVB-treated HaCaT cells via the activation of EMT.

Modifiable risk factors for thyroid cancer: lifestyle and residence environment.

In recent years, there has been a rapid increase in the prevalence of benign and malignant tumours of the thyroid gland worldwide, positioning it as one of the most prevalent neoplasms within the endocrine system. While the pathogenesis of thyroid tumours is still unclear, an increasing number of studies have found that certain lifestyle and residence environments are associated with their occurrence and development. This article endeavours to elucidate the correlation between lifestyle, residential environment, and the increased prevalence of thyroid cancer in recent years. It specifies the frequency of the lifestyle and outlines the scope of the residential environment. It also endeavours to summarise the main mechanistic pathways of various modifiable risk factors that cause thyroid cancer. Factors that prevent thyroid cancer include smoking and alcohol consumption, quality and regular sleep, consumption of cruciferous vegetables and dairy products, and consistent long-term exercise. Conversely, individuals with specific genetic mutations have an elevated risk of thyroid cancer from prolonged and frequent use of mobile phones. In addition, individuals who work in high-pressure jobs, work night shifts, and live near volcanoes or in environments associated with pesticides have an elevated risk of developing thyroid cancer. The impact of living near a nuclear power plant on thyroid cancer remains inconclusive. Raising awareness of modifiable risk factors for thyroid cancer will help to accurately prevent and control thyroid cancer. It will provide a scientific basis for future research on lifestyles and living environments suitable for people at high risk of thyroid cancer.

Abnormal Functional Asymmetry in the Salience and Auditory Networks in First-episode, Drug-naive Somatization Disorder.

Evidence of abnormal functional connectivity (FC) has been implicated in patients with somatization disorder (SD). Although the importance of damage to the functional asymmetry has been established, it remains unclear as to whether abnormal intra- and inter-hemispheric FCs are related to patients with SD. We applied resting-state functional magnetic resonance imaging to first-episode, medication-naive patients with SD (n = 25) and matched healthy controls (HCs) (n = 28). The data were analyzed using parameter of asymmetry (PAS) and support vector machine (SVM). Patients with SD showed significantly lower PAS values in the left inferior temporal gyrus (ITG) and higher PAS values in the right insula compared to HCs. A negative correlation was observed between the higher PAS values in the right insula and the Hamilton Depression Scale (HAMD) sleep subscale scores (r = -0.502, p = 0.011), and positive correlations were found between the lower PAS values in the left ITG and the Hamilton Anxiety Scale (HAMA) somatic anxiety subscale scores (r = 0.443, p = 0.027) and the HAMA total scores (r = 0.456, p = 0.022). Moreover, the increased PAS values in the right insula could distinguish patients with SD from HCs with acceptable accuracy (77.36%). First-episode, treatment-naive patients with SD show disrupted asymmetry of inter- and intra-hemispheric FCs. The pattern of disrupted functional asymmetry occurs early in the course of the disease and is independent of medication status, which suggests that disrupted functional asymmetry of salience and auditory networks may be applied as early biological markers for SD.

Effect of endoplasmic reticulum stress involved in manganese­induced neurotoxicity in rats.

The aim of the present study was to probe the mechanism of apoptosis induced by endoplasmic reticulum stress (ERS) in manganese­induced rats. A total of 60 Sprague­Dawley rats were randomly divided into a Vehicle group, LoMag group, HiMag group, and HiMag + 4­phenylbutyrate (PBA) group. Manganese content was measured by Inductively Coupled Plasma­Atomic Emission Spectrometry. Pathogenic morphology, the cellular structure of the striatum and ER were observed by hematoxylin and eosin staining and electron microscopy. The TUNEL method was used to examine neuronal apoptosis in the rat striatum. The expression levels of glucose­regulated protein 78KD (GRP78), C/EBP homologous protein (CHOP), c­Jun N­terminal kinase (JNK) and caspase­12 were analyzed by western blot analysis. The results revealed that striatal manganese concentrations in the LoMag and HiMag groups were higher than that in the Vehicle group (P<0.01). Rat striatal neuronal structure and apoptotic rates in the LoMag and HiMag groups were higher than those in the Vehicle group (P<0.05). 4­PBA treatment effectively reduced the apoptotic cell number (P<0.05). In addition, ER swelling and vacuolization in the HiMag + PBA group was reduced compared with that in the HiMag group. In addition, the protein expression levels of GRP78, CHOP, JNK and caspase­12 in the LoMag and HiMag groups were higher than those in the Vehicle group (P<0.05). However, the expression of these four proteins was reduced by 4­PBA treatment (P<0.05). In conclusion, 4­PBA significantly reduced the damage and apoptosis induced by manganese exposure in rats.