Oncolytic virotherapy evolved into the fourth generation as tumor immunotherapy.

BACKGROUND: Oncolytic virotherapy (OVT) is a promising anti-tumor modality that utilizes oncolytic viruses (OVs) to preferentially attack cancers rather than normal tissues. With the understanding particularly in the characteristics of viruses and tumor cells, numerous innovative OVs have been engineered to conquer cancers, such as Talimogene Laherparepvec (T-VEC) and tasadenoturev (DNX-2401). However, the therapeutic safety and efficacy must be further optimized and balanced to ensure the superior safe and efficient OVT in clinics, and reasonable combination therapy strategies are also important challenges worthy to be explored. MAIN BODY: Here we provided a critical review of the development history and status of OVT, emphasizing the mechanisms of enhancing both safety and efficacy. We propose that oncolytic virotherapy has evolved into the fourth generation as tumor immunotherapy. Particularly, to arouse T cells by designing OVs expressing bi-specific T cell activator (BiTA) is a promising strategy of killing two birds with one stone. Amazing combination of therapeutic strategies of OVs and immune cells confers immense potential for managing cancers. Moreover, the attractive preclinical OVT addressed recently, and the OVT in clinical trials were systematically reviewed. CONCLUSION: OVs, which are advancing into clinical trials, are being envisioned as the frontier clinical anti-tumor agents coming soon.

An enzyme activated fluorescent probe for LTA4H activity sensing and its application in cancer screening.

Early diagnosis of cancer is an efficient strategy to prevent tumor progression and improve the survival rate of patients. However, to discovery of reliable tumor-specific biomarkers remains a great challenge. Leukotriene A4 hydrolase (LTA4H) is a bifunctional zinc metalloenzyme with epoxide hydrolase activity and aminopeptidase activity, which plays important roles in allergic and inflammatory reactions and showed strong relevance with carcinoma progression. We thus sought to investigate the possibility of application LTA4H activity detection in cancer diagnosis. To achieve this, we herein develop an enzyme activated fluorescent probe for LTA4H activity sensing by incorporating the specific recognition unit of LTA4H with a red-emitting fluorophore. The acquired probe (named as ADMAB) showed high sensitivity and specificity toward LTA4H in vitro. By further application of ADMAB in living cells, significantly elevated LTA4H activity in cancer cell lines was observed when compared with normal cell lines and in vivo tracing A549 tumor in nude mice was also realized by ADMAB. Meanwhile, the wound-healing assay further revealed the importance of LTA4H in tumor metastasis. Moreover, the LTA4H activity in human serum sample was successfully detected by ADMAB and significantly elevated LTA4H activity in patients diagnosed with cancer was firstly found, which demonstrated ADMAB to be a useful tool for cancer diagnosis and LTA4H related biological study.

Aerobic exercise alleviates pyroptosis-related diseases by regulating NLRP3 inflammasome.

Pyroptosis plays a crucial role in a variety of human diseases, including atherosclerosis, obesity, diabetes, depression, and Alzheimer's disease, which usually release pyroptosis-related cytokines due to inflammation. Many studies have demonstrated that aerobic exercise is a good option for decreasing the release of pyroptosis-related cytokines. However, the molecular mechanisms of aerobic exercise on pyroptosis-related diseases remain unknown. In this review, the effects of aerobic exercise on pyroptosis in endothelial cells, adipocytes and hippocampal cells, and their potential mechanisms are summarized. In endothelial cells, aerobic exercise could inhibit NOD-like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis by improving the endothelial function, while reducing vascular inflammation and oxidative stress. In adipocytes, aerobic exercise has been shown to inhibit pyroptosis by ameliorating inflammation and insulin resistance. Moreover, aerobic exercise could restrict pyroptosis by attenuating microglial activation, neuroinflammation, and amyloid-beta deposition in hippocampal cells. In summary, aerobic exercise alleviates the pyroptosis-related diseases by regulating the NLRP3 inflammation si0067naling.

A novel "dual-locked" fluorescent probe for ONOO- and viscosity enables serum-based rapid disease screening.

Peroxynitrite (ONOO-) plays important roles in the progression of important disease such as inflammation, cancer, and diabetes, which made it an attractable target for biosensor development. However, to detect ONOO- solely is highly dependent on the sensitivity of the detection method and may be disturbed by unwillingly false-positive signal. Cellular viscosity is an important microenvironmental parameter and its abnormal changes are closely related to diseases such as diabetes and cancer. In this case, to construct a "dual-locked" molecular tool for both ONOO- and viscosity sensing and to evaluate the performance of such strategy in disease diagnosis is of great importance. We herein firstly reported the construction of a novel "dual-locked" probe DCI-OV which showed capability for simultaneous measuring ONOO- concentration and system viscosity with high sensitivity (LOD = 4.7 nM) and high specificity. Moreover, both exogenous and low level of endogenous ONOO- in living cells could be detected using DCI-OV due to viscosity amplified signal. Furthermore, cancer cells and insulin-resistant cells could be easily distinguished using DCI-OV. By taking advantage of the "dual-locked" sensing strategy, a total of 85 samples of human serum were screened using DCI-OV based rapid disease screening method and it was capable of differentiated and subdivided patients into specific type of disease, indicating the great potential of application of DCI-OV into clinical related disease diagnosis.