Jianming Cai

Ionizing radiation (IR) induced damages are common complications of radiotherapy for tumors, severely limiting the intensity and therapeutic efficacy of the radiotherapy program. Emerging data indicated that the cGAS‐STING pathway has paradoxical effects on IR‐induced damage. SR‐717, as a non‐nucleotide, small‐molecule stimulator of interferon genes (STING) agonist, has been proven that it could activate the STING signaling pathway. In this work, we try to explore the radioprotection of the STING signaling pathway and figure out whether SR‐717 could be a potential intestinal radioprotective agent. C57BL/6 mice were intraperitoneally treated with SR‐717 or normal saline (NS). By analyzing the survival rate, body weight, and the number of peripheral blood cells after IR exposure, we found that SR‐717 improved the survival rate and body weight of mice, protected the intestine from IR‐induced damage as well as hematopoietic damage, and promoted the regeneration of intestinal stem cells (ISCs). Cell viability and apoptosis after irradiation were detected after stimulation of MODE‐K cells with SR‐717 or PBS. We found that SR‐717 increased cell viability and inhibited apoptosis in vitro. The mechanism of SR‐717 in intestinal radiation protection was investigated by RNA‐seq. The results of RNA‐seq and qRT‐PCR suggested that SR‐717 significantly activated the immune system via the STING‐IL‐6 signaling pathway. In addition, we discussed the role of TLR2 in SR‐717‐mediated anti‐radiation activity, and TLR2 deletion significantly reversed the radioprotective effects of SR717. In conclusion, we proved STING signaling activation displayed anti‐radiation activity and found SR‐717 displayed anti‐radiation activity via the STING‐IL‐6 signaling pathway, suggesting SR‐717 could be a potential intestinal radioprotective agent.

Autophagy is an evolutionarily conserved process of cell self‐catabolism that provides a minimum level of energy for cellular homeostasis during metabolic stress. In radiotherapy (RT), it has been explicitly explained that autophagy plays a dual role in tumour control by tuning cellular radiosensitivity. However, the underlying molecular mechanism remains a conundrum. Therefore, it is of utmost importance to gain insight into the molecular mechanisms elaborating the autophagy‐mediated radiosensitivity and craft refined RT strategies for different tumours. Distinguishing it from previous reviews in the field, here we discuss the mechanisms of autophagy, especially its pro‐survival and growth‐suppressing mechanisms via regulation of radiosensitivity. We further outline some frontier RT adjuvant therapies targeting autophagy, in an endeavour to shed some light on the autophagy‐mediated pathways to harness radiosensitivity.

There is strong evidence connecting increased serum lipid levels to cardiovascular disorders, including atherosclerosis. Statins is prescribed as the primary medication to decrease lipid levels. Recent research has demonstrated that hydrogen possesses anti-inflammatory and antioxidant properties by modulating the expression of peroxisome proliferator-activated receptor gamma coactivator-1α, ultimately leading to the preservation of lipid homeostasis. Magnesium hydride (MgH₂) is a prolonged stable hydrogen storage medium, which can be utilized to investigate its synergistic lipid-lowering effect with statins and its detailed molecular mechanism, both in vivo and in vitro. To ascertain the safety and efficacy of MgH₂, we executed a comprehensive research of its influence on both physiological and pathological metrics. We noted a substantial diminution in lipid levels when MgH₂ was integrated with atorvastatin, as attested by oil red staining. Furthermore, we scrutinized the regulatory effect of MgH₂ on cytochrome P450 3A, which is a metabolic enzyme of statins, and discovered that it could be reduced by the MgH₂. Concluding from our results, we propose that MgH₂ inhibits the expression of cytochrome P450 3A in the liver and exerts an auxiliary lipid-lowering effect by increasing the blood concentration of statins. By augmenting our comprehension of MgH₂’s role in ameliorating lipid metabolism, we aspire to develop more promising therapies in the future.

Chronic kidney disease (CKD) poses a major global public health challenge. The World Health Organization’s data shows that CKD affects about 10% of the world’s population, particularly in low- and middle-income countries. Due to limited access to diagnosis and treatment, CKD has become the 12th leading cause of death worldwide. The advanced stage of CKD can lead to kidney failure, which is clinically referred to as end-stage renal disease (ESRD). In such cases, patients can only sustain life through dialysis or kidney transplantation. However, the long-term affordability of these treatments remains low. Moreover, the effectiveness of kidney transplantation is modest, posing a significant treatment barrier in resource-limited settings, and significantly impacting patient survival. To address this issue, we suggest using dietary supplementation of the trace element zinc to impede CKD development and prolong patient survival.

Purposes: Radiotherapy can induce tumor cell autophagy, which might impair the antitumoral effect. This study aims to investigate the effect of autophagy inhibition on the targeted radionuclide therapy (TRT) efficacy of ¹³¹I-FAP-2286 in pancreatic cancer. Methods: Human pancreatic cancer PANC-1 cells were exposed to ¹³¹I-FAP-2286 radiotherapy alone or with the autophagy inhibitor 3-MA. The autophagy level and proliferative activity of PANC-1 cells were analyzed. The pancreatic cancer xenograft-bearing nude mice were established by the co-injection of PANC-1 cells and pancreatic cancer-associated fibroblasts (CAFs), and then were randomly divided into four groups and treated with saline (control group), 3-MA, ¹³¹I-FAP-2286 and ¹³¹I-FAP-2286 + 3-MA, respectively. SPECT/CT imaging was performed to evaluate the bio-distribution of ¹³¹I-FAP-2286 in pancreatic cancer-bearing mice. The therapeutic effect of tumor was evaluated by ¹⁸F-FDG PET/CT imaging, tumor volume measurements, and the hematoxylin and eosin (H&E) staining, and immunohistochemical staining assay of tumor tissues. Results: ¹³¹I-FAP-2286 inhibited proliferation and increased the autophagy level of PANC-1 cells in a dose-dependent manner. 3-MA promoted ¹³¹I-FAP-2286-induced apoptosis of PANC-1 cells via suppressing autophagy. SPECT/CT imaging of pancreatic cancer xenograft-bearing nude mice showed that ¹³¹I-FAP-2286 can target the tumor effectively. According to ¹⁸F-FDG PET/CT imaging, the tumor growth curves and immunohistochemical analysis, ¹³¹I-FAP-2286 TRT was capable of suppressing the growth of pancreatic tumor accompanying with autophagy induction, but the addition of 3-MA enabled ¹³¹I-FAP-2286 to achieve a better therapeutic effect along with the autophagy inhibition. In addition, 3-MA alone did not inhibit tumor growth. Conclusions: ¹³¹I-FAP-2286 exposure induces the protective autophagy of pancreatic cancer cells, and the application of autophagy inhibitor is capable of enhancing the TRT therapeutic effect.

Background: Acquired radio-resistance and the undesired normal tissue radiation injuries seriously discount the therapeutic effect of lung cancer radiotherapy. In this study, we aimed to explore the role and potential mechanism of polydatin in simultaneously decreasing radioresistance and radiation injuries. Methods: The tumor-bearing model of nude mice was used to investigate the tumor inhibition of polydatin on lung cancer and its effect on radiosensitivity, and the effect of polydatin on B cell infiltration in cancerous tissue was investigated. In addition, we performed systemic radiotherapy on BABL/C mice and evaluated the protective effect of polydatin on radiation injury by the Kaplan–Meier survival curve. Moreover, the regulation of polydatin on proliferation and apoptosis of A549 cells was also investigated in vitro. Results: In this study, it is first found that polydatin inhibits the growth and promotes the radiosensitivity of lung cancer while reducing the radiation damage of the healthy tissue. Further, it is evidenced that the major mechanism relies on its regulation on body’s immune function, and in particular, the inhibition of radiation-induced B cell infiltration in tumor tissue. Conclusion: These findings show that in addition to tumor inhibition, polydatin also promotes the sensitivity and reduces the adverse reactions of radiotherapy, making itself a promising candidate for boosting lung cancer radiotherapy efficacy.

Background: Acquired radioresistanceand the undesired normal tissue radiation injuriesseriously discount the therapeutic effect of lung cancer radiotherapy. In this study, we aimed to explore the role and potential mechanism of polydatin in simultaneously decreasing radioresistance and radiation injuries. Methods: The tumor-bearing model of nude mice were used to investigate the tumor inhibition of polydatin on lung cancer and its effect on radiosensitivity, and the effect of polydatin on B cell infiltration in cancerous tissue was investigated. In addition, we performed systemic radiotherapy on BABL/ C mice and evaluated the protective effect of polydatin on radiation injury by the Kaplan-meier survival curve. Moreover, the regulation of polydatin on proliferation and apoptosis of A549 cells was also investigated in vitro. Results: In this study, it is firstly found that polydatin inhibits the growth and promotes the radiosensitivity of lung cancer while reducing the radiation damage of the healthy tissue. Further, it is evidenced that the major mechanism relies on its regulation on body’s immune function, and in particular, the inhibition of radiation-induced B cell infiltration in tumor tissue. Conclusion: These findings show that in addition to tumor inhibition, polydatin also promotes the sensitivity and reduces the adverse reactions of radiotherapy, making itself a promising candidate for boosting lung cancer radiotherapy efficacy.