Significance and limitations of routine p16/Ki-67 immunohistochemistry as a diagnostic tool for high-grade squamous intraepithelial lesions of the uterine cervix.

Objective: To evaluate the diagnostic utility and limitations of routine p16 and Ki-67 immunohistochemistry (IHC) in detecting high-grade squamous intraepithelial lesions (HSILs) in the uterine cervix.

Methods: We reviewed 2,061 cervical biopsy records, including 271 morphologically indeterminate squamous lesions, evaluated using p16/Ki-67 IHC for HSIL detection or exclusion. HSIL was diagnosed based on p16 positivity and a high Ki-67 labeling index (Ki-LI).

Microsomal Prostaglandin E Synthase-1 Controls Colonic Prostaglandin E Production and Exerts a Protective Effect on Colitis Induced by Trinitrobenzene Sulfonic Acid in Mice.

Microsomal prostaglandin E synthase-1 (mPGES-1) is an isozyme of the prostaglandin (PG) E synthase that acts downstream of cyclooxygenase and catalyzes the conversion of PGH to PGE. The impact of genetic deletion of mPGES-1 on the development of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis, a well-established model of inflammatory bowel disease (IBD), was investigated in this study. After administration of TNBS, mice deficient in mPGES-1 (mPGES-1 mice) showed more severe colitis than did wild-type (WT) mice.

SARS-CoV-2 propagation to the TPH2-positive neurons in the ventral tegmental area induces cell death via GSK3β-dependent accumulation of phosphorylated tau.

COVID-19, an infectious disease caused by SARS-CoV-2, was declared a pandemic by the WHO in 2020. Psychiatric symptoms including sleep disturbance, memory impairment, and depression are associated with SARS-CoV-2 infection. These symptoms are causes long-term mental and physical distress in recovering patients; however, the underlying mechanism is unclear.

Mechanistic exploration of bioactive constituents in Gnetum gnemon for GPCR-related cancer treatment through network pharmacology and molecular docking.

G Protein-Coupled Receptors (GPCRs) are integral membrane proteins that have gained considerable attention as drug targets, particularly in cancer treatment. In this study, we explored the capacity of bioactive compounds derived from Gnetum gnemon (GG) for the development of of pharmaceuticals targeting GPCRs within the context of cancer therapy. Integrated approach combined network pharmacology and molecular docking to identify and validate the underlying pharmacological mechanisms.

The Roles of Mitochondria in Human Being's Life and Aging.

The universe began 13.8 billion years ago, and Earth was born 4.6 billion years ago.

Hypoglycemic activity of L. extracts on diabetes rodent models: A systematic review and network meta-analysis.

Background: Diabetes mellitus is a significant global health issue, and alternative treatments from natural products like L. [Clusiaceae] or GM are being explored for their potential benefits. This study focused on evaluating the hypoglycemic effects of GM on diabetic rodent models.

T-cell Large Granular Lymphocytic Leukemia with a STAT3 mutation successfully treated with Cord Blood Transplantation.

A 64-year-old woman presented with agranulocytosis, anemia, and bacteremia, leading to a diagnosis of T-cell large granular lymphocytic leukemia (T-LGLL). A molecular analysis identified a signal transducer and activator of transcription 3 (STAT3) Y640F variant. Initial treatment with cyclophosphamide and prednisolone did not improve her condition, but serious infections were observed.

Changes in rotator movement during early gait acquisition in after total hip arthroplasty.

Background: In walking in healthy adults, rotation of the hip joint affects stride length and shifts the center of gravity, but these are not seen in hip osteoarthritis which affects gait. In gait of total hip arthroplasty, there are few reports on changes in the horizontal plane. This study clarified the preoperative and early postoperative gait characteristics of patients undergoing total hip arthroplasty.

Biphenotypic Cells and α-Synuclein Accumulation in Enteric Neurons of Leucine-Rich Repeat Kinase 2 Knockout Mice.

Background: Leucine-rich repeat kinase 2 is a molecule that is responsible for familial Parkinson's disease. Our previous findings revealed that leucine-rich repeat kinase 2 is expressed in the enteric nervous system. However, which cells in the enteric nervous system express leucine-rich repeat kinase 2 and whether leucine-rich repeat kinase 2 is associated with the structure of the enteric nervous system remain unclear.

Leaf extract of promotes anti-heat stress and antioxidant effects in .

has been used for traditional medicines, healthy foods and tea. The chemical compositions and biological activities of fruit, stem bark and root have been widely studied. However, the phytochemical components and the biological activities in leaves (GAL) are limited.

Concordance Between Biopsy and Resection Diagnoses of Uterine Cervical Adenocarcinoma According to the Updated World Health Organization 2020 Classification: A Multi-Institutional Study Elucidating Real-World Practice in Japan.

Context.—: Endocervical adenocarcinoma is divided into human papillomavirus (HPV)-associated (HPVA) and HPV-independent (HPVI) in the 5th edition of the World Health Organization (WHO) tumor classification launched in 2020. However, the validity of the morphologic criteria used for biopsy specimens in real-world practice remains undetermined.

Mitochondria Play Essential Roles in Intracellular Protection against Oxidative Stress-Which Molecules among the ROS Generated in the Mitochondria Can Escape the Mitochondria and Contribute to Signal Activation in Cytosol?

Questions about which reactive oxygen species (ROS) or reactive nitrogen species (RNS) can escape from the mitochondria and activate signals must be addressed. In this study, two parameters, the calculated dipole moment (debye, D) and permeability coefficient (Pm) (cm s), are listed for hydrogen peroxide (HO), hydroxyl radical (•OH), superoxide (O), hydroperoxyl radical (HO•), nitric oxide (•NO), nitrogen dioxide (•NO), peroxynitrite (ONOO), and peroxynitrous acid (ONOOH) in comparison to those for water (HO). O is generated from the mitochondrial electron transport chain (ETC), and several other ROS and RNS can be generated subsequently.

Mitochondrial oxidative stress, mitochondrial ROS storms in long COVID pathogenesis.

Significance: This review discusses the coronavirus disease 2019 (COVID-19) pathophysiology in the context of diabetes and intracellular reactions by COVID-19, including mitochondrial oxidative stress storms, mitochondrial ROS storms, and long COVID.

Recent Advances: The long COVID is suffered in ~10% of the COVID-19 patients. Even the virus does not exist, the patients suffer the long COVID for even over a year, This disease could be a mitochondria dysregulation disease.

LRRK2 negatively regulates glucose tolerance via regulation of membrane translocation of GLUT4 in adipocytes.

Epidemiological studies have shown that abnormalities of glucose metabolism are involved in leucine-rich repeat kinase 2 (LRRK2)-associated Parkinson's disease (PD). However, the physiological significance of this association is unclear. In the present study, we investigated the effect of LRRK2 on high-fat diet (HFD)-induced glucose intolerance using Lrrk2-knockout (KO) mice.

Interleukin-13 Mediates Non-Steroidal Anti-Inflammatory-Drug-Induced Small Intestinal Mucosal Injury with Ulceration.

Non-steroidal anti-inflammatory drugs (NSAIDs), which are antipyretics and analgesics, cause gastrointestinal disorders, such as inflammation and ulcers. To prescribe NSAIDs more safely, it is important to clarify the mechanism of NSAID-induced gastrointestinal mucosal injury. However, there is a paucity of studies on small intestinal mucosal damage by NSAIDs, and it is currently unknown whether inflammation and ulceration also occur in the small intestine, and whether mediators are involved in the mechanism of injury.

Assessment of eight insulin resistance surrogate indexes for predicting metabolic syndrome and hypertension in Thai law enforcement officers.

Police officers in Thailand have an increased risk of heart disease, stroke, and type 2 diabetes, possibly due to a high prevalence of hypertension and metabolic syndrome (MetS). In this study, the researchers aimed to understand the relationship between surrogate markers of insulin resistance (IR) and the prevalence of MetS and hypertension in Thai police officers. The study included 7,852 police officer participants, of which 91.

Comprehensive Cancer Genomic Profiling of Liver Metastasis Led to the Unexpected Identification of Colorectal Cancer.

Comprehensive genomic profiling (CGP) of a metastatic liver tumor biopsy specimen suggested that the patient, who was initially diagnosed with cholangiocarcinoma, had colorectal cancer. The identification of both FBXW7 and APC mutations is deemed characteristic of colorectal cancer. Indeed, subsequent colonoscopy revealed sigmoid colon carcinoma that led to tumor resection followed by systemic chemotherapy.

Evidence of Nrf2/Keap1 Signaling Regulation by Mitochodria-Generated Reactive Oxygen Species in RGK1 Cells.

It has been known that reactive oxygen species (ROS) are generated from the mitochondrial electron transport chain (ETC). Majima et al. proved that mitochondrial ROS (mtROS) caused apoptosis for the first time in 1998 (Majima et al.