Deubiquitinating enzymes: potential regulators of the tumor microenvironment and implications for immune evasion.

Ubiquitination and deubiquitination are important forms of posttranslational modification that govern protein homeostasis. Deubiquitinating enzymes (DUBs), a protein superfamily consisting of more than 100 members, deconjugate ubiquitin chains from client proteins to regulate cellular homeostasis. However, the dysregulation of DUBs is reportedly associated with several diseases, including cancer.

Preparation, Swelling, and Drug Release Studies of Chitosan-based Hydrogels for Controlled Delivery of Buspirone Hydrochloride.

Background: Buspirone is used for the management of depression and anxiety disorders. Due to its short half-life and low bioavailability, it requires multiple daily doses and is associated with some side effects.

Aim: This study aimed to develop chitosan-based hydrogels as drug-controlled release carriers.

Fabrication and Evaluation of Carbopol/Polyvinyl Alcohol-based pH-sensitive Hydrogels for Controlled Drug Delivery.

Background: Diclofenac sodium has a short half-life (about 1.5 hours), requiring repeated administration, and as a result, serious complications, such as GI bleeding, peptic ulcer, and kidney and liver dysfunction, are generated. Hence, a sustained/controlled drug delivery system is needed to overcome the complications caused by the administration of diclofenac sodium.

Synthesis and Evaluation of Alginate-Based Nanogels as Sustained Drug Carriers for Caffeine.

The objective of this study is to design a polymeric network of nanogels for sustained release of caffeine. Therefore, alginate-based nanogels were fabricated by a free-radical polymerization technique for the sustained delivery of caffeine. Polymer alginate was crosslinked with monomer 2-acrylamido-2-methylpropanesulfonic acid by crosslinker ','-methylene bisacrylamide.

XPF-ERCC1 Blocker Improves the Therapeutic Efficacy of 5-FU- and Oxaliplatin-Based Chemoradiotherapy in Colorectal Cancer.

5-FU-based chemoradiotherapy (CRT) and oxaliplatin-based CRT are commonly used therapies for advanced colorectal cancer (CRC). However, patients with a high expression of ERCC1 have a worse prognosis than those with a low expression. In this study, we investigated the effect of XPF-ERCC1 blockers on chemotherapy and 5-FU-based CRT and oxaliplatin (OXA)-based CRT in colorectal cancer cell lines.

The Pyroptotic and Nonpyroptotic Roles of Gasdermins in Modulating Cancer Progression and Their Perspectives on Cancer Therapeutics.

Gasdermins (GSDMs) are a protein family encoded by six paralogous genes in humans, including GSDMA, GSDMB, GSDMC, GSDMD, GSDME (also known as DFNA5), and DFNB59 (also known as pejvakin). Structurally, members of the GSDM family possess a C-terminus (an autoinhibitory domain) and a positively charged N-terminus (a pore-forming domain) linked with divergent peptide linkers. Recently, GSDMs have been identified as key executors of pyroptosis (an immunogenic programmed cell death) due to their pore-forming activities on the plasma membrane when proteolytically cleaved by caspases or serine proteases.

Improvement in Skin Penetration Capacity of Linalool by Using Microemulsion as a Delivery Carrier: Formulation Optimization and In Vitro Evaluation.

Linalool is an aromatic oil with analgesic, anti-inflammatory and anti-UVB-induced skin damage effects. The aim of this study was to develop a linalool-loaded microemulsion formulation for topical application. In order to quickly obtain an optimal drug-loaded formulation, statistical tools of the response surface methodology and a mixed experimental design with four independent variables of oil (X), mixed surfactant (X), cosurfactant (X) and water (X) were used to design a series of model formulations in order to analyze the effect of the composition on the characteristics and permeation capacity of linalool-loaded microemulsion formulations and to obtain an appropriate drug-loaded formulation.

Diphenyl disulfide potentiates the apoptosis of breast cancer cells through Bax proteolytic activation with accompanying autophagy.

Breast cancer is a leading cause of cancer-related death worldwide, and chemoresistance often leads to poor patient outcomes. In this study, we investigated the anticancer activity of synthetic diphenyl disulfide (DPDS) in breast cancer cell lines. DPDS inhibited cellular proliferation and viability in a dose-dependent manner and reduced colony formation, an index of clonogenicity.

ATG4B and pS383/392-ATG4B serve as potential biomarkers and therapeutic targets of colorectal cancer.

Background: Autophagy related protease 4B (ATG4B) is a protease required for autophagy processing, which is strongly implicated in cancer progression.  Phosphorylation of ATG4B is crucial for activation of its protease activity.  However, little is known about the relationship of ATG4B and its phosphorylated form at Ser 383 and 392 sites (pS383/392-ATG4B), with clinical outcomes, particularly in colorectal cancer (CRC).

The Role of Exosomes in Pancreatic Ductal Adenocarcinoma Progression and Their Potential as Biomarkers.

Pancreatic ductal adenocarcinoma (PDAC), the most common pancreatic malignancy, is an aggressive and lethal cancer with a dismal five-year survival rate. Despite remarkable improvements in cancer therapeutics, the clinical outcome of PDAC patients remains poor due to late diagnosis of the disease. This highlights the importance of early detection, wherein biomarker evaluation including exosomes would be helpful.

Designing and In Vitro Characterization of pH-Sensitive Aspartic Acid-Graft-Poly(Acrylic Acid) Hydrogels as Controlled Drug Carriers.

Acetaminophen is an odorless and white crystalline powder drug, used in the management of fever, pain, and headache. The half-life of acetaminophen is very short; thus, multiple intakes of acetaminophen are needed in a day to maintain a constant pharmacological action for an extended period of time. Certain severe adverse effects are produced due to the frequent intake of acetaminophen, especially hepatotoxicity and skin rashes.

In Vitro Evaluation of Smart and pH-Sensitive Chondroitin Sulfate/Sodium Polystyrene Sulfonate Hydrogels for Controlled Drug Delivery.

Ibuprofen is an antipyretic and analgesic drug used for the management of different inflammatory diseases, such as rheumatoid arthritis and osteoarthritis. Due to a short half-life and rapid elimination, multiple doses of ibuprofen are required in a day to maintain pharmacological action for a long duration of time. Due to multiple intakes of ibuprofen, certain severe adverse effects, such as gastric irritation, bleeding, ulcers, and abdominal pain are produced.

Inflammation-related pyroptosis, a novel programmed cell death pathway, and its crosstalk with immune therapy in cancer treatment.

In recent decades, chemotherapies targeting apoptosis have emerged and demonstrated remarkable achievements. However, emerging evidence has shown that chemoresistance is mediated by impairing or bypassing apoptotic cell death. Several novel types of programmed cell death, such as ferroptosis, necroptosis, and pyroptosis, have recently been reported to play significant roles in the modulation of cancer progression and are considered a promising strategy for cancer treatment.

The association between hepatitis C virus infection and renal function.

Background: The association between hepatitis C virus (HCV) infection and chronic kidney disease (CKD) still remains controversial. We aimed to investigate whether HCV really affects renal function, and to analyze the association between clinical effects of CHC and decreased kidney function (assessed by glomerular filtration rate (eGFR) level).

Methods: An estimated 3360 patients with HCV infection and 3360 age- and sex-matched community-based control individuals without HCV were enrolled (1:1, case and control ratio) in this study between 2004 and 2016.

Antilingula as a Surgical Reference Point for Vertical Ramus Osteotomy.

Purpose: This study investigated the antilingula and its related landmarks, the mandibular rami, by using cone-beam computed tomography (CBCT).

Methods: CBCT images of 37 patients (74 sides of the mandibular ramus) were collected. The landmarks of antilingula (AntiL), anterior ramus (A), posterior ramus (P), superior ramus (S), and inferior ramus (I) were identified.

Sagittal Split Ramus Osteotomy in the Shortest Buccal Bone Marrow Distances of the Mandible on the Coronal Plane.

Purpose: This study investigated the relationship between the shortest buccal bone marrow of the ramus and skeletal patterns.

Materials And Methods: Using cone-beam computed tomography data (specifically, the A point-nasion-B point (ANB) angle), we divided patients into three groups as follows: skeletal class I (0° < ANB < 4°), class II (ANB: ≥4°), and class III (ANB: ≤0°). Sixteen vertical sections in the coronal plane were taken starting from slice 0 (original intact mandibular canal) anteriorly at 2 mm intervals to slice 15 (30 mm).

Activities of imipenem-relebactam combination against carbapenem-nonsusceptible Enterobacteriaceae in Taiwan.

Background: Imipenem-relebactam is a new β-lactam and β-lactamase inhibitor combination to treat carbapenem-resistant gram-negative bacteria infections. However, difference in carbapenem resistant mechanisms existed with geographic variations.

Objective: To evaluate the susceptibility of imipenem-relebactam to 660 carbapenem-nonsusceptible Enterobacteriaceae isolates in Taiwan and to identify the in vivo efficacy with a Caenorhabditis elegans model.

Curcumin Metabolite Tetrahydrocurcumin in the Treatment of Eye Diseases.

Curcumin is one of the most valuable natural products due to its pharmacological activities. However, the low bioavailability of curcumin has long been a problem for its medicinal use. Large studies have been conducted to improve the use of curcumin; among these studies, curcumin metabolites have become a relatively new research focus over the past few years.

In Vitro and In Vivo Evaluations of β-Lactam/β-Lactamase Mono- and Combined Therapies against Carbapenem-Nonsusceptible Enterobacteriaceae in Taiwan.

Increasing carbapenem resistance rates worldwide underscored the urgent need of novel antimicrobials. Ceftazidime-avibactam and aztreonam-avibactam combinations are developed to combat carbapenem resistance, but biological and geographic variations must be considered for antibiotic susceptibility patterns varied. Thus, we sought to assess the susceptibilities of ceftazidime-avibactam and aztreonam-avibactam against 660 carbapenem-nonsusceptible Enterobacteriaceae isolates (472 and 188 ) collected during an earlier Taiwan surveillance study.

An Increased Plasma Level of ApoCIII-Rich Electronegative High-Density Lipoprotein May Contribute to Cognitive Impairment in Alzheimer's Disease.

High-density lipoprotein (HDL) plays a vital role in lipid metabolism and anti-inflammatory activities; a dysfunctional HDL impairs cholesterol efflux pathways. To understand HDL's role in patients with Alzheimer's disease (AD), we analyzed the chemical properties and function. HDL from AD patients (AD-HDL) was separated into five subfractions, H1-H5, using fast-protein liquid chromatography equipped with an anion-exchange column.

Gel-Based Nanocarrier for Intravesical Chemotherapy Delivery: In Vitro and In Vivo Study.

Intravesical administration of chemotherapeutic agents can enhance drug accumulation in tumors and reduce systemic side effects. Nanocarriers were developed for intravesical administration and exploit the permeation enhancement effect. In vitro permeation evaluation, the drug transdermal amount and accumulation amounts in the tissue of gemcitabine-loaded nanocarriers through biological membrane significantly increased about 14.

Direct Binding of Cisplatin to p22phox, an Endoplasmic Reticulum (ER) Membrane Protein, Contributes to Cisplatin Resistance in Oral Squamous Cell Carcinoma (OSCC) Cells.

Prolonged treatment with cisplatin (CDDP) frequently develops chemoresistance. We have previously shown that p22phox, an endoplasmic reticulum (ER) membrane protein, confers CDDP resistance by blocking CDDP nuclear entry in oral squamous cell carcinoma (OSCC) cells; however, the underlying mechanism remains unresolved. Using a fluorescent dye-labeled CDDP, here we show that CDDP can bind to p22phox in both cell-based and cell-free contexts.

The Role of Necroptosis in ROS-Mediated Cancer Therapies and Its Promising Applications.

Over the past decades, promising therapies targeting different signaling pathways have emerged. Among these pathways, apoptosis has been well investigated and targeted to design diverse chemotherapies. However, some patients are chemoresistant to these therapies due to compromised apoptotic cell death.

Autophagy Is Deficient and May be Negatively Regulated by SERPINB3 in Middle Ear Cholesteatoma.

Hypothesis: Whereas autophagy has been linked to various human diseases, whether it also plays a role in cholesteatoma is virtually unknown. This study aimed to investigate the activity and regulation of autophagy in cholesteatoma.

Background: The treatment of middle ear cholesteatoma has been challenging due to an insufficient understanding of the underlying disease mechanism.