Differences in ocular adverse events associated with phosphodiesterase-5 inhibitors: a real-world pharmacovigilance study.

Objective: Our study aims to characterize the ocular safety profiles of phosphodiesterase type 5 (PDE5) inhibitors and explore the differences among different PDE5 inhibitors.

Methods: We analyzed reports on ocular adverse events associated with sildenafil, vardenafil and tadalafil submitted to the FDA Adverse Event Reporting System (FAERS) database from the first quarter of 2004 to the first quarter of 2023. Disproportionality analysis was conducted to evaluate reporting risk profiles.

immunotherapy combined with gemcitabine has a synergistic inhibitory effect on tumor growth and metastasis in murine Lewis lung cancer models.

Objective: Our previous studies have demonstrated that immunotherapy (infection) has antitumor effects in mice. However, as a new form of immunotherapy, this therapy has a weakness: its specific killing effect on tumor cells is relatively weak. Therefore, we tested whether immunotherapy combined with gemcitabine (Gem), a representative chemotherapy drug, has synergistic antitumor effects.

Application of Monocyte-to-Albumin Ratio and Neutrophil Percentage-to-Hemoglobin Ratio on Distinguishing Non-Small Cell Lung Cancer Patients from Healthy Subjects.

Objective: This study aims at assessing the potential benefits of observation of monocyte-to-albumin ratio (MAR) and neutrophil percentage-to-hemoglobin ratio (NPHR) in the detection of non-small cell lung cancer (NSCLC).

Methods: This study retrospectively involved 195 NSCLC patients and 204 healthy volunteers. The correlations between the clinicopathological characteristics of NSCLC and the two ratios including MAR and NPHR were assessed.

Circular RNA DHTKD1 targets miR‑338‑3p/ETS1 axis to regulate the inflammatory response in human bronchial epithelial cells.

Asthma is a chronic inflammatory airway disease and the airway epithelium is involved in airway inflammation and innate immunity. However, whether circular RNA (circRNA) is involved in the pathogenesis of asthma remains unclear. The present study aimed to determine the functions and molecular mechanisms of circRNA targeting dehydrogenase E1 (circDHTKD1) in the inflammation response of human bronchial epithelial cells.

Exogenous melatonin enhances tomato heat resistance by regulating photosynthetic electron flux and maintaining ROS homeostasis.

Heat stress reduces plant growth and reproduction and increases agricultural risks. As a natural compound, melatonin modulates broad aspects of the responses of plants to various biotic and abiotic stresses. However, regulation of the photosynthetic electron transfer, reactive oxygen species (ROS) homeostasis and the redox state of redox-sensitive proteins in the tolerance to heat stress induced by melatonin remain largely unknown.

Preclinical Study of Immunotherapy Combined with Radiotherapy for Solid Tumors.

Immune checkpoint blockade therapy (ICB) is ineffective against cold tumors and, although it is effective against some hot tumors, drug resistance can occur. We have developed a immunotherapy (PI) that can overcome these shortcomings. However, the specific killing effect of PI on tumor cells is relatively weak.

An automated heart rate-based algorithm for sleep stage classification: Validation using conventional polysomnography and an innovative wearable electrocardiogram device.

Background: The rapid advancement in wearable solutions to monitor and score sleep staging has enabled monitoring outside of the conventional clinical settings. However, most of the devices and algorithms lack extensive and independent validation, a fundamental step to ensure robustness, stability, and replicability of the results beyond the training and testing phases. These systems are thought not to be feasible and reliable alternatives to the gold standard, polysomnography (PSG).

Subsequent malaria enhances virus-specific T cell immunity in SIV-infected Chinese rhesus macaques.

Background: Coinfection with HIV and Plasmodium parasites is fairly common, but the sequence of infection with these two pathogens and their impact on disease progression are poorly understood.

Methods: A Chinese rhesus macaque HIV and Plasmodium coinfection model was established to compare the impact of pre-existing and subsequent malaria on the progression of SIV infection.

Results: We found that a pre-existing malaria caused animals to produce a greater number of CD4CCR5 T cells for SIV replication, resulting in higher viral loads.

Preparation of Decoquinate Solid Dispersion by Hot-Melt Extrusion as an Oral Dosage Form Targeting Liver-Stage Infection.

Liver-stage in humans is an early stage of malarial infection. Decoquinate (DQ) has a potent multistage antimalarial activity. However, it is practically water insoluble.

Decoquinate liposomes: highly effective clearance of Plasmodium parasites causing severe malaria.

Background: Severe malaria caused by Plasmodium falciparum leads to most malaria-related deaths globally. Decoquinate (DQ) displays strong activity against multistage infection by Plasmodium parasites. However, the development of DQ as an oral dosage form for the treatment of malaria at the blood stage has not been successful.

infection prevents recurrence and metastasis of hepatocellular carcinoma possibly via inhibition of the epithelial‑mesenchymal transition.

Postoperative recurrence causes a high mortality rate among patients with hepatocellular carcinoma (HCC). The current study aimed to determine the effects of infection on HCC metastasis and recurrence. The antitumor effects of infection were determined using two murine orthotopic HCC models: The non‑resection model and the resection model.

Plasmodium infection inhibits triple negative 4T1 breast cancer potentially through induction of CD8 T cell-mediated antitumor responses in mice.

We previously reported that Plasmodium infection promotes antitumor immunity in a murine Lewis lung cancer. In this study, we investigated the effects of Plasmodium infection on the tumor inhibition and antitumor CD8 T cell responses in a murine triple negative breast cancer (TNBCA) model. The results showed that Plasmodium infection significantly inhibited tumor growth, and increased the survival rate of the tumor-bearing mice.

Plasmodium infection inhibits tumor angiogenesis through effects on tumor-associated macrophages in a murine implanted hepatoma model.

Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death in China. The lack of an effective treatment for this disease results in a high recurrence rate in patients who undergo radical tumor resection, and the 5-year survival rate of these patients remains low. Our previous studies demonstrated that Plasmodium infection provides a potent antitumor effect by inducing innate and adaptive immunity in a murine Lewis lung carcinoma (LLC) model.

Experimental Treatment of SIV-Infected Macaques via Autograft of -Disrupted Hematopoietic Stem and Progenitor Cells.

Hematopoietic stem cell (HSC)-based gene therapy targeting represents a promising way to cure human immunodeficiency virus type 1 (HIV-1) infection. Yet the preclinical animal model with transplantation of autologous -ablated HSCs remains to be optimized. In this study, four Chinese rhesus macaques of simian immunodeficiency virus (SIV) chronic infection were given long-term antiretroviral therapy (ART), during which peripheral CD34 hematopoietic stem and progenitor cells (HSPCs) were purified and infected with -specific CRISPR/Cas9 lentivirus (three monkeys) or GFP lentivirus (one monkey).

4-Aryl Pyrrolidines as Novel Orally Efficacious Antimalarial Agents. Part 2: 2-Aryl--(4-arylpyrrolidin-3-yl)acetamides.

Malaria is caused by infection from the parasite and kills hundreds of thousands of people every year. Emergence of new drug resistant strains of demands identification of new drugs with novel chemotypes and mechanisms of action. As a follow up to our evaluation of 4-aryl--benzylpyrrolidine-3-carboxamides as novel pyrrolidine-based antimalarial agents, we describe herein the structure-activity relationships of the reversed amide homologues 2-aryl--(4-arylpyrrolidin-3-yl)acetamides.

Plasmodium infection inhibits the expansion and activation of MDSCs and Tregs in the tumor microenvironment in a murine Lewis lung cancer model.

Background: A major challenge in the development of effective cancer immunotherapy is the ability of tumors and their microenvironment to suppress immune cells through immunosuppressive cells such as myeloid -derived suppressor cells and regulatory T cells. We previously demonstrated that Plasmodium infection promotes innate and adaptive immunity against cancer in a murine Lewis lung cancer model but its effects on immunosuppressive cells in the tumor microenvironment are unknown.

Methods: Whole Tumors and tumor-derived sorted cells from tumor-bearing mice treated with or without plasmodium infected red blood cells were harvested 17 days post tumor implantation and analyzed using QPCR, western blotting, flow cytometry, and functional assays.

4-Aryl Pyrrolidines as a Novel Class of Orally Efficacious Antimalarial Agents. Part 1: Evaluation of 4-Aryl- N-benzylpyrrolidine-3-carboxamides.

Identification of novel chemotypes with antimalarial efficacy is imperative to combat the rise of Plasmodium species resistant to current antimalarial drugs. We have used a hybrid target-phenotype approach to identify and evaluate novel chemotypes for malaria. In our search for drug-like aspartic protease inhibitors in publicly available phenotypic antimalarial databases, we identified GNF-Pf-4691, a 4-aryl- N-benzylpyrrolidine-3-carboxamide, as having a structure reminiscent of known inhibitors of aspartic proteases.

Granuloma formation in the liver is relatively delayed, although sustained, in BCG‑infected mice co‑infected with Plasmodium.

The purpose of the present study was to examine the effects of Plasmodium on the process of granuloma formation in Bacille Calmette‑Guerin (BCG)‑infected mice. Female six‑week‑old BALB/c mice were co‑infected with BCG and Plasmodium. The liver index, pathological alterations and quantity of granulomas in the mice were observed when the mice were co‑injected with BCG and Plasmodium.

Simultaneous Knockout of CXCR4 and CCR5 Genes in CD4+ T Cells via CRISPR/Cas9 Confers Resistance to Both X4- and R5-Tropic Human Immunodeficiency Virus Type 1 Infection.

Previous research has proven that disruption of either the CCR5 or the CXCR4 gene confers resistance to R5-tropic or X4-tropic human immunodeficiency virus type 1 (HIV-1) infection, respectively. However, the urgent need to ablate both of the co-receptors in individual post-thymic CD4+ T cells for dual protection remains. This study ablated the CCR5 and CXCR4 genes in human CD4+ cell lines and primary CD4+ T cells simultaneously using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9, a well-developed, highly efficient genetic engineering tool.

Plasmodium parasite as an effective hepatocellular carcinoma antigen glypican-3 delivery vector.

We have previously demonstrated that malaria parasite infection has an anti-tumor effect in a mouse model. This research aimed to investigate the possibility of using Plasmodium parasite as a novel vaccine vector for hepatocellular carcinoma (HCC) immunotherapy. We constructed a Plasmodium yoelii 17XNL strain (P.

Worldwide malaria incidence and cancer mortality are inversely associated.

Background: Investigations on the effects of malaria infection on cancer mortality are limited except for the incidence of Burkitt's lymphoma (BL) in African children. Our previous murine lung cancer model study demonstrated that malaria infection significantly inhibited tumor growth and prolonged the life span of tumor-bearing mice. This study aims to assess the possible associations between malaria incidence and human cancer mortality.