Biperiden and mepazine effectively inhibit MALT1 activity and tumor growth in pancreatic cancer

MALT1 is a key mediator of NF-κB signaling and a main driver of B-cell lymphomas. Remarkably, MALT1 is expressed in the majority of pancreatic ductal adenocarcinomas (PDACs) as well, but absent from normal exocrine pancreatic tissue. Following, MALT1 shows off to be a specific target in cancer cells of PDAC without affecting regular pancreatic cells. Therefore, we studied the impact of pharmacological MALT1 inhibition in pancreatic cancer and showed promising effects on tumor progression. Mepazine (Mep), a phenothiazine derivative, is a known potent MALT1 inhibitor. Newly, we described that biperiden (Bip) is a potent MALT1 inhibitor with even less pharmacological side effects. Thus, Bip is a promising drug leading to reduced proliferation and increased apoptosis in PDAC cells in vitro and in vivo. By compromising MALT1 activity, nuclear translocation of c-Rel is prevented. c-Rel is critical for NF-κB-dependent inhibition of apoptosis. Hence, off-label use of Bip or Mep represents a promising new therapeutic approach to PDAC treatment. Regularly, the Anticholinergicum Bip is used to treat neurological side effects of Phenothiazines, like extrapyramidal symptoms.     

Telematics-based online client–server/client collaborative environment for radiotherapy planning simulations

Customized cancer radiation treatment planning for each patient is very useful for both a patient and a doctor because it provides the ability to deliver higher doses to a more accurately defined tumor and at the same time lower doses to organs at risk and normal tissues. This can be realized by building an accurate planning simulation system to provide better treatment strategies based on each patient’s tomographic data such as CT, MRI, PET, or SPECT. In this study, we develop a real-time online client–server/client collaborative environment between the client (health care professionals or hospitals) and the server/client under a secure network using telematics (the integrated use of telecommunications and medical informatics). The implementation is based on a point-to-point communication scheme between client and server/client following the WYSIWIS (what you see is what I see) paradigm. After uploading the patient tomographic data, the client is able to collaborate with the server/client for treatment planning. Consequently, the level of health care services can be improved, specifically for small radiotherapy clinics in rural/remote-country areas that do not possess much experience or equipment such as a treatment planning simulator. The telematics service of the system can also be used to provide continued medical education in radiotherapy. Moreover, the system is easy to use. A client can use the system if s/he is familiar with the Windows^TM operating system because it is designed and built based on a user-friendly concept. This system does not require the client to continue hardware and software maintenance and updates. These are performed automatically by the server.     

Type I interferons have opposing effects during the emergence and recovery phases of colitis

The contribution of the innate immune system to inflammatory bowel disease (IBD) is under intensive investigation. Research in animal models has demonstrated that type I interferons (IFN‐Is) protect from IBD. In contrast, studies of patients with IBD have produced conflicting results concerning the therapeutic potential of IFN‐Is. Here, we present data suggesting that IFN‐Is play dual roles as regulators of intestinal inflammation in dextran sodium sulfate (DSS)‐treated C57BL/6 mice. Though IFN‐Is reduced acute intestinal damage and the abundance of colitis‐associated intestinal bacteria caused by treatment with a high dose of DSS, they also inhibited the resolution of inflammation after DSS treatment. IFN‐Is played an anti‐inflammatory role by suppressing the release of IL‐1β from the colon MHC class II⁺ cells. Consistently, IL‐1 receptor blockade reduced the severity of inflammation in IFN‐I receptor‐deficient mice and myeloid cell‐restricted ablation of the IFN‐I receptor was detrimental. The proinflammatory role of IFN‐Is during recovery from DSS treatment was caused by IFN‐I‐dependent cell apoptosis as well as an increase in chemokine production and infiltrating inflammatory monocytes and neutrophils. Thus, IFN‐Is play opposing roles in specific phases of intestinal injury and inflammation, which may be important for guiding treatment strategies in patients.     

Early life stress-induced neuroinflammation and neurological disorders:a novel perspective for research

Childhood maltreatment(CM)has been consistently linked with numerous detrimental outcomes concerning physical and psychological health.However,few studies have explored vulnerability to neurological disorders after CM.Early life adversity,in the form of poverty,stress and abuse,has been associated with decline in cognitive function and dementia later in life(Short and Baram,2019).Robust preclinical data suggest that early life stress(ELS)may increase the risk and worsen the course of neurological disorders such as Alzheimer’s(AD)and Parkinson’s(PD)diseases,and traumatic brain injury(TBI)(Lesuis et al.,2018;Short and Baram,2019;He et al.,2020;Catale et al.,2021;Sanchez et al.,2021).     

Predictive Factors for Conversion of Laparoscopic Cholecystectomy

Reliable predictive factors for conversion of laparoscopic cholecystectomy (LC) would be extremely useful in the preparation and planning of admission for patients with symptomatic cholelithiasis. Data from 783 patients in whom LC was attempted in a university clinic from June 1990 to December 1995 were retrospectively analyzed. The aim of this study was to determine preoperative indicators that can be useful for predicting conversion to open cholecystectomy (OC). Conversion was required in 58 (7.4%) patients, of which 48 (83%) were elective and 10 (17%) emergency. Factors evaluated were age, sex, obesity, duration of gallstone disease, co-morbid factors, indication for surgery, previous abdominal surgery, fever, physical examination findings, white blood cell (WBC) count, liver function tests, ultrasound findings, and the experience of the surgeon. Acute cholecystitis, rigidity in the right upper abdomen, fever, thickened gallbladder wall on ultrasonography, elevated alkaline phosphatase (ALP), liver transaminases and the WBC count were significant predictors of conversion in the univariate analysis. Multivariate logistic regression analysis on these significant predictors showed that acute cholecystitis [odds ratio (OR) = 3.12], thickened gallbladder wall on ultrasonography (OR = 3.75), elevated ALP (OR = 2.23), and WBC count (OR = 3.69) were jointly significant.     

Incidence of Cancer Following Bariatric Surgery: Systematic Review and Meta-analysis

Obesity is linked to the development of cancer. Previous studies have suggested that there is a relationship between bariatric surgery and reduced cancer risk. Data sources were from Medline, Embase, and Cochrane Library. From 951 references, 13 studies met the inclusion criteria (54,257 participants). In controlled studies, bariatric surgery was associated with a reduction in the risk of cancer. The cancer incidence density rate was 1.06 cases per 1000 person-years within the surgery groups. In the meta-regression, we found an inverse relationship between the presurgical body mass index and cancer incidence after surgery (beta coefficient ?0.2, P?相似文献