Efficacy and safety of YOXINTINE for depression: A double-blinded, randomized, placebo-controlled, phase 2 clinical trial.

Background: YOXINTINE contains >98 % of 20(S)-protopanaxadial (PPD), a metabolic product of ginsenosides with pre-clinical neuroprotective activity. Animal experiments and previous studies have shown that PPD has good antidepressant effect and safety.

Purpose: To evaluate YOXINTINE in treating depression compared with a placebo in Chinese patients.

A Novel Self-Amplifying mRNA with Decreased Cytotoxicity and Enhanced Protein Expression by Macrodomain Mutations.

The efficacy and safety of self-amplifying mRNA (saRNA) have been demonstrated in COVID-19 vaccine applications. Unlike conventional non-replicating mRNA (nrmRNA), saRNA offers a key advantage: its self-replication mechanism fosters efficient expression of the encoded protein, leading to substantial dose savings during administration. Consequently, there is a growing interest in further optimizing the expression efficiency of saRNA.

Oncolytic virotherapy stimulates anti‑tumor immune response and demonstrates activity in advanced sarcoma: Report of two cases.

Sarcoma is derived from mesenchymal neoplasms and has numerous subtypes, accounting for 1% of all adult malignancies and 15% of childhood malignancies. The prognosis of metastatic or recurrent sarcoma remains poor. The current study presents two cases of sarcoma enrolled in a phase I dose escalation trial for solid tumor, who had previously failed all standard therapies.

Prevention and treatment of HPV-related cancer through a mRNA vaccine expressing APC-targeting antigen.

Persistent human papillomavirus (HPV) infection is associated with multiple malignancies. Developing therapeutic vaccines to eliminate HPV-infected and malignant cells holds significant value. In this study, we introduced a lipid nanoparticle encapsulated mRNA vaccine expressing tHA-mE7-mE6.

Prophylactic Vaccination and Intratumoral Boost with HER2-Expressing Oncolytic Herpes Simplex Virus Induces Robust and Persistent Immune Response against HER2-Positive Tumor Cells.

The development of effective cancer vaccines remains a significant challenge due to immune tolerance and limited clinical benefits. Oncolytic herpes simplex virus type 1 (oHSV-1) has shown promise as a cancer therapy, but efficacy is often limited in advanced cancers. In this study, we constructed and characterized a novel oHSV-1 virus (VG22401) expressing the human epidermal growth factor receptor 2 (HER2), a transmembrane glycoprotein overexpressed in many carcinomas.

mRNA vaccines encoding fusion proteins of monkeypox virus antigens protect mice from vaccinia virus challenge.

The recent outbreaks of mpox have raised concerns over the need for effective vaccines. However, the current approved vaccines have either been associated with safety concerns or are in limited supply. mRNA vaccines, which have shown high efficacy and safety against SARS-CoV-2 infection, are a promising alternative.

Vaccines' New Era-RNA Vaccine.

RNA vaccines, including conventional messenger RNA (mRNA) vaccines, circular RNA (circRNA) vaccines, and self-amplifying RNA (saRNA) vaccines, have ushered in a promising future and revolutionized vaccine development. The success of mRNA vaccines in combating the COVID-19 pandemic caused by the SARS-CoV-2 virus that emerged in 2019 has highlighted the potential of RNA vaccines. These vaccines possess several advantages, such as high efficacy, adaptability, simplicity in antigen design, and the ability to induce both humoral and cellular immunity.

Targeting carcinoembryonic antigen-expressing tumors using a novel transcriptional and translational dual-regulated oncolytic herpes simplex virus type 1.

VG2025 is a recombinant oncolytic herpes simplex virus type 1 (HSV-1) that uses transcriptional and translational dual regulation (TTDR) of critical viral genes to enhance virus safety and promote tumor-specific virus replication without reducing virulence. The TTDR platform is based on transcriptional control of the essential HSV-1 immediate-early protein ICP27 using a tumor-specific carcinoembryonic antigen (CEA) promoter, coupled with translational control of the neurovirulence factor ICP34.5 using multiple microRNA (miR)-binding sites.

Heterologous boost with mRNA vaccines against SARS-CoV-2 Delta/Omicron variants following an inactivated whole-virus vaccine.

The coronavirus SARS-CoV-2 has mutated quickly and caused significant global damage. This study characterizes two mRNA vaccines ZSVG-02 (Delta) and ZSVG-02-O (Omicron BA.1), and associating heterologous prime-boost strategy following the prime of a most widely administrated inactivated whole-virus vaccine (BBIBP-CorV).

Pre-Existing HSV-1 Immunity Enhances Anticancer Efficacy of a Novel Immune-Stimulating Oncolytic Virus.

Oncolytic viruses (OVs) can specifically replicate in the host and cause cancer cell lysis while inducing an antitumor immune response. The aim of this study is to investigate the impact of either pre-existing immunity against herpes simplex virus type-1 (HSV-1) or multicycle treatment with OVs on anticancer efficacy of VG161, an HSV-1 OV in phase 2 clinical trial. VG161 efficacy was tested in CT26 mouse models by comparing the efficacy and immune response in naïve mice or in mice that were immunized with VG161.

Enhanced genomic stability of new miRNA-regulated oncolytic coxsackievirus B3.

Genetic modification of coxsackievirus B3 (CVB3) by inserting target sequences (TS) of tumor-suppressive and/or organ-selective microRNAs (miRs) into viral genome can efficiently eliminate viral pathogenesis without significant impacts on its oncolytic activity. Nonetheless, reversion mutants (loss of miR-TS inserts) were identified as early as day 35 post-injection in ∼40% immunodeficient mice. To improve the stability, here we re-engineered CVB3 by (1) replacing the same length of viral genome at the non-coding region with TS of cardiac-selective miR-1/miR-133 and pancreas-enriched miR-216/miR-375 or (2) inserting the above miR-TS into the coding region (i.

Erratum: MicroRNA Modification of Coxsackievirus B3 Decreases Its Toxicity, while Retaining Oncolytic Potency against Lung Cancer.

[This corrects the article DOI: 10.1016/j.omto.

Induction of Durable Antitumor Response by a Novel Oncolytic Herpesvirus Expressing Multiple Immunomodulatory Transgenes.

Oncolytic virotherapy is a promising new tool for cancer treatment, but direct lytic destruction of tumor cells is not sufficient and must be accompanied by strong immune activation to elicit anti-tumor immunity. We report here the creation of a novel replication-competent recombinant oncolytic herpes simplex virus type 1 (VG161) that carries genes coding for IL-12, IL-15, and IL-15 receptor alpha subunit, along with a peptide fusion protein capable of disrupting PD-1/PD-L1 interactions. The VG161 virus replicates efficiently and exhibits robust cytotoxicity in multiple tumor cell lines.

Oncolytic virotherapy in hepato-bilio-pancreatic cancer: The key to breaking the log jam?

Traditional therapies have limited efficacy in hepatocellular carcinoma, pancreatic cancer, and biliary tract cancer, especially for advanced and refractory cancers. Through a deeper understanding of antitumor immunity and the tumor microenvironment, novel immunotherapies are becoming available for cancer treatment. Oncolytic virus (OV) therapy is an emerging type of immunotherapy that has demonstrated effective antitumor efficacy in many preclinical studies and clinical studies.

MicroRNA Modification of Coxsackievirus B3 Decreases Its Toxicity, while Retaining Oncolytic Potency against Lung Cancer.

We recently discovered that coxsackievirus B3 (CVB3) is a potent oncolytic virus against mutant lung adenocarcinoma. Nevertheless, the evident toxicity restricts the use of wild-type (WT)-CVB3 for cancer therapy. The current study aims to engineer the CVB3 to decrease its toxicity and to extend our previous research to determine its safety and efficacy in treating / mutant small-cell lung cancer (SCLC).

Exploratory examination of inflammation state, immune response and blood cell composition in a human obese cohort to identify potential markers predicting cancer risk.

Obesity has reached epidemic proportions and is often accompanied by elevated levels of pro-inflammatory cytokines that promote many chronic diseases, including cancer. However, not all obese people develop these diseases and it would be very helpful to identify those at high risk early on so that preventative measures can be instituted. We performed an extensive evaluation of the effects of obesity on inflammatory markers, on innate and adaptive immune responses, and on blood cell composition to identify markers that might be useful in distinguishing those at elevated risk of cancer.

Coxsackievirus Type B3 Is a Potent Oncolytic Virus against -Mutant Lung Adenocarcinoma.

mutant ( ) lung adenocarcinoma is a refractory cancer without available targeted therapy. The current study explored the possibility to develop coxsackievirus type B3 (CVB3) as an oncolytic agent for the treatment of lung adenocarcinoma. In cultured cells, we discovered that CVB3 selectively infects and lyses lung adenocarcinoma cells (A549, H2030, and H23), while sparing normal lung epithelial cells (primary, BEAS2B, HPL1D, and 1HAEo) and lung adenocarcinoma cells (HCC4006, PC9, H3255, and H1975).

UV Light-inactivated HSV-1 Stimulates Natural Killer Cell-induced Killing of Prostate Cancer Cells.

Herein we demonstrate that ultraviolet light-inactivated Herpes Simplex Virus-1 (UV-HSV-1) stimulates peripheral blood mononuclear cells (PBMCs) to lyse both androgen-sensitive and androgen-independent prostate cancer (PrCA) cell lines, but not the benign prostatic hyperplastic epithelial cell line, BPH-1, and is 1000-10,000-fold more potent at stimulating this killing than ultraviolet light-inactivated Vesicular Stomatitis Virus, adenovirus, reovirus or cytomegalovirus. Among PBMCs, natural killer (NK) cells appear to be a major cell type involved in this killing and UV-HSV-1 appears to directly and potently stimulate NK cell expression of CD69, degranulation, cytokine production, and migration to IL-8 in PC3 conditioned medium. We also found that UV-HSV-1 stimulates glycolysis in PBMCs and NK cells, and that 2-deoxyglucose and the protein kinase C inhibitor, Go6976, and the NFκB inhibitor, Bay 11-7082, all abrogate UV-HSV-1 activated killing of PC3 cells by PBMCs and NK cells.

20(S)-protopanaxadiol regio-selectively targets androgen receptor: anticancer effects in castration-resistant prostate tumors.

We have explored the effects of 20(S)-protopanaxadiol (aPPD), a naturally derived ginsenoside, against androgen receptor (AR) positive castration resistant prostate cancer (CRPC) xenograft tumors and have examined its interactions with AR. docking studies for aPPD binding to AR, alongside transactivation bioassays and efficacy studies were carried out in the castration-resistant C4-2 xenograft model. Immunohistochemical (IHC) and Western blot analyses followed by evaluation of AR, apoptotic, cell cycle and proliferative markers in excised tumors was performed.

A TRAMP-derived orthotopic prostate syngeneic (TOPS) cancer model for investigating anti-tumor treatments.

Background: Patients with advanced prostate cancer have limited curative options, therefore new treatments are needed. Mouse models play a pivotal role in the discovery and development of new treatments. In the present study, a TRAMP-derived Orthotopic Prostate Syngeneic (TOPS) mouse model was developed and found to provide a consistent means of monitoring tumor and metastatic responses to novel treatments.

Caspase independent cleavages of TDP-43 generates 35kD fragment that cause apoptosis of breast cancer cells.

Transactive response DNA-binding protein 43kD (TDP-43) is a major component of tau-negative and ubiquitin-positive inclusions that characterize ALS (amyotrophic lateral sclerosis) and FTLD (frontotemporal lobar degeneration). Due to its central role in neurodegenerative disease pathogenesis, most research recently has focused on its role associated with neurodegeneration disease, research on neuron and glial cell showed that pathological TDP-43 is associated with cell apoptosis which lead to loss of functional neurons and glial cells. However, little is known about its role on cancer cells, here we report a 35kD fragment of TDP-43 also plays a key role in apoptosis of breast cancer cells, and may be served as a potential therapeutic target to cure cancer.

Effect of age on chronic inflammation and responsiveness to bacterial and viral challenges.

To identify reliable biomarkers of age-related changes in chronic inflammation and responsiveness to bacterial and viral challenges, we evaluated endogenous and ex vivo stimulated levels of 18 inflammatory markers, using whole blood collected in EDTA and sodium heparin tubes from 41 healthy volunteers, i.e., 11 men + 10 women aged 20-35 and 10 men + 10 women aged 50-77.

Oncolytic Virotherapy Blockade by Microglia and Macrophages Requires STAT1/3.

The first oncolytic virotherapy employing HSV-1 (oHSV-1) was approved recently by the FDA to treat cancer, but further improvements in efficacy are needed to eradicate challenging refractory tumors, such as glioblastomas (GBM). Microglia/macrophages comprising approximately 40% of a GBM tumor may limit virotherapeutic efficacy. Here, we show these cells suppress oHSV-1 growth in gliomas by internalizing the virus through phagocytosis.

Circadian Rhythm Regulates Development of Enamel in Mouse Mandibular First Molar.

Rhythmic incremental growth lines and the presence of melatonin receptors were discovered in tooth enamel, suggesting possible role of circadian rhythm. We therefore hypothesized that circadian rhythm may regulate enamel formation through melatonin receptors. To test this hypothesis, we examined expression of melatonin receptors (MTs) and amelogenin (AMELX), a maker of enamel formation, during tooth germ development in mouse.