Increased Apolipoprotein A1 Expression Correlates with Tumor-Associated Neutrophils and T Lymphocytes in Upper Tract Urothelial Carcinoma.

An increased neutrophil-to-lymphocyte ratio (NLR) is a poor prognostic biomarker in various types of cancer, because it reflects the inhibition of lymphocytes in the circulation and tumors. In urologic cancers, upper tract urothelial carcinoma (UTUC) is known for its aggressive features and lack of T cell infiltration; however, the association between neutrophils and suppressed T lymphocytes in UTUC is largely unknown. In this study, we examined the relationship between UTUC-derived factors and tumor-associated neutrophils or T lymphocytes. The culture supernatant from UTUC tumor tissue modulated neutrophils to inhibit T cell proliferation. Among the dominant factors secreted by UTUC tumor tissue, apolipoprotein A1 (Apo-A1) exhibited a positive correlation with NLR. Moreover, tumor-infiltrating neutrophils were inversely correlated with tumor-infiltrating T cells. Elevated Apo-A1 levels in UTUC were also inversely associated with the population of tumor-infiltrating T cells. Our findings indicate that elevated Apo-A1 expression in UTUC correlates with tumor-associated neutrophils and T cells. This suggests a potential immunomodulatory effect on neutrophils and T cells within the tumor microenvironment, which may represent therapeutic targets for UTUC treatment.

Design and Synthesis of Novel Chalcone Derivatives: Anti-Breast Cancer Activity Evaluation and Docking Study.

Chalcone is a common simple fragment of natural products with anticancer activity. In a previous study, the research group discovered a series of chalcone derivatives with stronger anticancer activities. To find better anticancer drugs, novel chalcone derivatives A1-A14, B1-B14 have continuously been designed and synthesized. The antiproliferative activity of these compounds against breast cancer cells (MCF-7) was investigated by the Cell Counting Kit-8 (CCK-8) method with 5-fluorouracil (5-Fu) as the control drug. The results showed that compound A14 exhibited excellent antiproliferative ability compared to the control drug 5-Fu. Scratch experiments and cloning experiments further confirmed that compound A14 could inhibit the proliferation and colony formation activity of MCF-7 cells. In addition, molecular docking primarily explains the interaction between compound and protein. These results suggested that compound A14 could be a promising chalcone derivative for further anti-breast cancer research.

Early phase oncology clinical trials in Malaysia: current status and future perspectives.

Historically, the majority of oncology clinical trials are conducted in Western Europe and North America. Globalization of drug development has resulted in sponsors shifting their focus to the Asia-Pacific region. In Malaysia, implementation of various government policies to promote clinical trials has been initiated over a decade ago and includes the establishment of Clinical Research Malaysia, which functions as a facilitator and enabler of industry-sponsored clinical trials on a nationwide basis. Although oncology clinical trials in Malaysia have seen promising growth, there are still only a limited number of early phase oncology studies being conducted. Hence, the Phase 1 Realization Project was initiated to develop Malaysia's early phase clinical trial capabilities. In addition, the adaptation of good practices from other countries contribute to the effective implementation of existing initiatives to drive progress in the development of early phase drug development set up in Malaysia. Furthermore, holistic approaches with emphasis in training and education, infrastructure capacities, strategic alliances, reinforcement of upstream activities in the value chain of drug development, enhanced patient advocacy, coupled with continued commitment from policy makers are imperative in nurturing a resilient clinical research ecosystem in Malaysia.

On-Resin Synthesis of Linear Aryl Thioether Containing Peptides and in-Solution Cyclization via Cysteine SNAr Reaction.

Cyclic peptides represent one of the most promising therapeutic agents in drug discovery due to their good affinity and selectivity. Herein, an on-resin synthesis of aryl thioether containing peptides and a concise cyclization strategy via chemoselective cysteine SNAr reaction was developed. The arylation group could be incorporated into a series of amino acids and used for standard SPPS and peptides cyclization. Constructed cyclic peptides showed increased cellular uptakes compared to their linear peptides.

Peptide-guided JC polyomavirus-like particles specifically target bladder cancer cells for gene therapy.

The ultimate goal of gene delivery vectors is to establish specific and effective treatments for human diseases. We previously demonstrated that human JC polyomavirus (JCPyV) virus-like particles (VLPs) can package and deliver exogenous DNA into susceptible cells for gene expression. For tissue-specific targeting in this study, JCPyV VLPs were conjugated with a specific peptide for bladder cancer (SPB) that specifically binds to bladder cancer cells. The suicide gene thymidine kinase was packaged and delivered by SPB-conjugated VLPs (VLP-SPBs). Expression of the suicide gene was detected only in human bladder cancer cells and not in lung cancer or neuroblastoma cells susceptible to JCPyV VLP infection in vitro and in vivo, demonstrating the target specificity of VLP-SPBs. The gene transduction efficiency of VLP-SPBs was approximately 100 times greater than that of VLPs without the conjugated peptide. JCPyV VLPs can be specifically guided to target particular cell types when tagged with a ligand molecule that binds to a cell surface marker, thereby improving gene therapy.

Uniform Polypyrrole Layer-Coated Sulfur/Graphene Aerogel via the Vapor-Phase Deposition Technique as the Cathode Material for Li-S Batteries.

The practical application of Li-S batteries is hampered because of their poor cycling stability caused by electrolyte-dissolved lithium polysulfides. Dual functionalities such as strong chemical adsorption stability and high conductivity are highly desired for an ideal host material for the sulfur-based cathode. Herein, a uniform polypyrrole layer-coated sulfur/graphene aerogel composite is designed and synthesized using a novel vapor-phase deposition method. The polypyrrole layer simultaneously acts as a host and an adsorbent for efficient suppression of polysulfide dissolution through strong chemical interaction. The density functional theory calculations reveal that the polypyrrole could trap lithium polysulfides through stronger bonding energy. In addition, the deflation of sulfur/graphene hydrogel during the vapor-phase deposition process enhances the contact of sulfur with matrices, resulting in high sulfur utilization and good rate capability. As a result, the synthesized polypyrrole-coated sulfur/graphene aerogel composite delivers specific discharge capacities of 1167 and 409.1 mA h g-1 at 0.2 and 5 C, respectively. Moreover, the composite can maintain a capacity of 698 mA h g-1 at 0.5 C after 500 cycles, showing an ultraslow decay rate of 0.03% per cycle.

Nickel sulfide nanocrystals on nitrogen-doped porous carbon nanotubes with high-efficiency electrocatalysis for room-temperature sodium-sulfur batteries.

Polysulfide dissolution and slow electrochemical kinetics of conversion reactions lead to low utilization of sulfur cathodes that inhibits further development of room-temperature sodium-sulfur batteries. Here we report a multifunctional sulfur host, NiS2 nanocrystals implanted in nitrogen-doped porous carbon nanotubes, which is rationally designed to achieve high polysulfide immobilization and conversion. Attributable to the synergetic effect of physical confinement and chemical bonding, the high electronic conductivity of the matrix, closed porous structure, and polarized additives of the multifunctional sulfur host effectively immobilize polysulfides. Significantly, the electrocatalytic behaviors of the Lewis base matrix and the NiS2 component are clearly evidenced by operando synchrotron X-ray diffraction and density functional theory with strong adsorption of polysulfides and high conversion of soluble polysulfides into insoluble Na2S2/Na2S. Thus, the as-obtained sulfur cathodes exhibit excellent performance in room-temperature Na/S batteries.

Robot-Assisted Retroperitoneoscopic Surgery for Synchronous Contralateral Ureteral Metastasis of Renal-Cell Carcinoma.

Renal-cell carcinoma (RCC) with synchronous metastasis to contralateral ureter is extremely rare with only four cases reported in the literature. We report a case of synchronous metastatic RCC to the contralateral ureter with effective robot-assisted retroperitoneoscopic nephron-sparing surgery that leads to favorable oncologic and functional outcome.

Resolvin D1, an endogenous lipid mediator for inactivation of inflammation-related signaling pathways in microglial cells, prevents lipopolysaccharide-induced inflammatory responses.

BACKGROUNDS AND AIM: Microglial cells as an important part of central nervous system (CNS) have generally believed to play significant role in the process leading to a number of neurodegenerative disorders including Parkinson's disease, Alzheimer's disease, prion diseases, multiple sclerosis, HIV-dementia, and stroke. Although different diseases have quite different pathogenesis, the activation of microglia was shared with all of them. Recently, the resolvin D1 (RvD1) as an endogenous antiinflammatory lipid mediator has been confirmed to be involved in the treatment of inflammation-related neuronal injury in neurodegenerative diseases. Therefore, the inhibition of microglia-activated inflammation has been considered as a major treatment strategy in neurodegenerative disease therapy. However, the molecular mechanisms of RvD1 in microglial cells remain unknown and still do not be reported. METHODS: We taken murine microglia as the experimental sample, and Western blotting, ELISA, reverse-transcriptase PCR, real-time PCR, and electrophoretic mobility shift assay were used to study whether the RvD1 inhibit inflammation of microglial cells. The tumor necrosis factor α (TNF-α), IL-1ß, inducible nitric oxide synthase (iNOS) expression, nuclear factor-κB (NF-κB) activation, and mitogen-activated protein kinase (MAPK) pathways were investigated in lipopolysaccharide (LPS)-activated primary microglia. RESULTS: Our data suggested that RvD1 inhibited the production of LPS-induced microglia inflammatory mediators and TNF-α, IL-1ß, and iNOS expression. In addition, according to the study of related signaling pathways, RvD1 attenuated LPS-induced microglia NF-κB activation,MAPK phosphorylation, and activator protein-1 transcriptional activity. CONCLUSION: This is the first study to demonstrate that RvD1 effects on the reduction of pro-inflammatory responses in LPS-induced microglial cells. The mechanisms underlying these effects may include its potent intracellular NF-κB down-regulation and subsequent pro-inflammatory cytokines release in LPS-activated microglia.

Inhibition of human immunodeficiency virus type 1 entry by a binding domain of Porphyromonas gingivalis gingipain.

Human immunodeficiency virus (HIV) transmission through saliva is extremely low. Several oral components, including secretory immunoglobulin A and secretory leukocyte protease inhibitor, are known as potential inhibitory agents of HIV oral transmission. Here we examined anti-HIV activity of oral bacterial components. We showed that recombinant protein HGP44 derived from Porphyromonas gingivalis, one of the primary infectious agents of periodontitis, was capable of inhibiting HIV type 1 (HIV-1) replication. HGP44 bound specifically to HIV-1 gp120 and blocked HIV-1 envelope-mediated membrane fusion. These findings suggest that HGP44 of P. gingivalis can inhibit HIV-1 infection by blocking HIV-1 entry.