Advances in Nanotechnology for Enhancing the Solubility and Bioavailability of Poorly Soluble Drugs.

This manuscript offers a comprehensive overview of nanotechnology's impact on the solubility and bioavailability of poorly soluble drugs, with a focus on BCS Class II and IV drugs. We explore various nanoscale drug delivery systems (NDDSs), including lipid-based, polymer-based, nanoemulsions, nanogels, and inorganic carriers. These systems offer improved drug efficacy, targeting, and reduced side effects. Emphasizing the crucial role of nanoparticle size and surface modifications, the review discusses the advancements in NDDSs for enhanced therapeutic outcomes. Challenges such as production cost and safety are acknowledged, yet the potential of NDDSs in transforming drug delivery methods is highlighted. This contribution underscores the importance of nanotechnology in pharmaceutical engineering, suggesting it as a significant advancement for medical applications and patient care.

Hepatocytes-derived Prdx1 regulates macrophage phenotypes via TLR4 activation in acute liver injury.

Acute liver injury (ALI) is a significant causative factor for multiple hepatic diseases. The excessive inflammatory response triggers proinflammatory immune cells recruitment, infiltration and differentiation, further contributing to inflammatory injuries in liver. As a proinflammatory factor, circulating Peroxiredoxin 1 (Prdx1) is elevated in ALI patients and mice. In this study, through carbon tetrachloride (CCl4) and cecal puncture and ligation (CLP)-induced liver injury mice model, we found hepatocytes-derived Prdx1 expression was increased in ALI. After AAV8-Prdx1-mediated Prdx1 knockdown, CCl4 and CLP-induced ALI was alleviated, along with the reduced proinflammatory cytokines, suppressed myeloid cells recruitment, decreased proportions of hepatic macrophages and neutrophils, restrained proinflammatory macrophage differentiation and infiltration. Mechanistically, hepatocyte-derived Prdx1 regulated macrophages through paracrine activation of the TLR4 signal. Our data support the immune and inflammatory regulatory role of Prdx1 in ALI pathological process to suggest its potential therapeutic application and clinical value.

Study from the United States: increased prevalence of kidney stones in patients with high weight-adjusted waist index.

Objective: Using data from NHANES 2007-2018, to examine the association between WWI (weight-adjusted waist index) index and prevalence of kidney stones. Methods: Using multiple logistic regression analysis of the National Health and Nutrition Examination Survey (NHANES) 2007-2018, we evaluated the association between WWI index and the prevalence of kidney stones, followed by subgroup analysis of sensitive populations. Smooth curve fitting was used to determine whether there was a non-linear relationship between the WWI index and kidney stone prevalence, and threshold effect analysis was used to test this relationship. Results: Among 29,280 participants, 2,760 self-reported renal calculi. After adjustment for all confounders, there was a positive association between WWI and kidney stone prevalence (OR = 1.20, 95% CI: 1.12, 1.28), and this positive association was stronger with increasing WWI (and P = 0.01 for trend). Our results indicate a non-linear positive correlation between WWI index and kidney stones, with the saturation threshold effect analysis and the most important threshold value at 11.02. According to subgroup analysis, WWI showed the strongest association with kidney stone prevalence in participants aged 20-39 years, males, other US ethnic groups, and participants without hypertension and diabetes. Conclusion: Increased WWI is positively associated with increased incidence of kidney stones, and increased WWI is a high risk for kidney stones that should be treated with caution. This association should be more pronounced in people between the ages of 20 and 39 years, in men, in other US ethnic populations, and in participants who do not have hypertension or diabetes.

KLF2-induced circZKSCAN1 potentiates the tumorigenic properties of clear cell renal cell carcinoma by targeting the miR-1294/PIM1 axis.

Clear cell renal cell carcinoma (ccRCC) is one of the most common and lethal types of urologic cancer. With low survival rates among patients in advanced stages of disease, and increasing rate of morbidity and mortality worldwide, novel therapeutic targets for ccRCC clinical intervention are necessary. In this study, we investigated the functional role of circZKSCAN1 in ccRCC progression. Our results suggested that circZKSCAN1 was abundantly expressed in ccRCC tumor tissues and cells. CircZKSCAN1 knockdown significantly inhibited cell proliferation, migration, invasion, and epithelial-to-mesenchymal transition of renal cell carcinoma (RCC) cells, whereas potentiated Natural Killer (NK) cell-mediated cytotoxicity against RCC cells in vitro and repressed tumor growth in vivo. Furthermore, we identified a novel circZKSCAN1/miR-1294/PIM1 axis was identified in RCC progression, showing that the expression of circZKSCAN1 expression in RCC cells was transcriptionally regulated by Kruppel-like factor 2. The results of our study may provide new insights for ccRCC basic research.Abbreviations: ccRCC: clear cell renal cell carcinoma; ChIP: chromatin immunoprecipitation; circRNA: circular RNA; EDU: 5-ethynyl-2'-deoxyuridine; EMT: epithelial-mesenchymal transition; FBS: fetal bovine serum; FISH: RNA fluorescent in situ hybridization; KLF2: Kruppel-like factor 2; NC: normal control; NK cell: natural killer cell; NOD/SCID: nonobese severe diabetic/severe combined immunodeficiency; PIM1: Pim-1 proto-oncogene, serine/threonine kinase; RCC: renal cell carcinoma; ZKSCAN1: zinc finger with KRAB and SCAN domains 1.

Aberrant activation of Wnt/catenin signaling and overexpression of ABCG2 contributes to apoptosis down regulation and tumor progression of high grade ovarian cancer.

Side Population (SP) cells are the small pool of CSC like progenitor cells, which are drug resistant and recapitulate tumor generation. The occurrence of SP cells is the major inference for attaining a better treatment and improved patient survival. In this work, we have isolated 6% SP cells from a high grade ovarian carcinoma. Our functional characterization of SP cells revealed that elevated ABCG2 and anti-apoptotic factors contribute to chemoresistance and increased life span of SP cells. Further, the overexpression of surface antigens, such as CD133 and CD117 in SP cells, are the key driving forces for high clonogenic and invasion properties of SP cells. More importantly, we found by RT-PCR aberrant activation and upregulation of Wnt/ ß-catenin and its downstream targeting genes, such as DKK1 and AXIN2 in SP cells. These findings suggest that development of new anticancer drugs which target Wnt/ß-catenin signaling might effectively exterminate the SP cells and aid in disease free survival.