Efficacy and safety of immune checkpoint inhibitors with or without radiotherapy in metastatic non-small cell lung cancer: A systematic review and meta-analysis.

Although immune checkpoint inhibitors (ICIs) have become the first-line treatment for metastatic non-small cell lung cancer (mNSCLC), their efficacy is limited. Meanwhile, recent reports suggest that radiotherapy (RT) can activate the systemic antitumor immune response by increasing the release of antigens from tumor tissues. Therefore, in patients with mNSCLC treated with ICIs, investigations were performed to determine whether the addition of RT improved the outcomes.

Mechanism, Prevention, and Treatment of Radiation-Induced Salivary Gland Injury Related to Oxidative Stress.

Radiation therapy is a common treatment for head and neck cancers. However, because of the presence of nerve structures (brain stem, spinal cord, and brachial plexus), salivary glands (SGs), mucous membranes, and swallowing muscles in the head and neck regions, radiotherapy inevitably causes damage to these normal tissues. Among them, SG injury is a serious adverse event, and its clinical manifestations include changes in taste, difficulty chewing and swallowing, oral infections, and dental caries.

Effect of Dapagliflozin on Intestinal Flora in MafA-deficient Mice.

Objective: To investigate the effect of dapagliflozin on intestinal microflora in MafA-deficient mice using an animal model of diabetes.

Methods: Male MafA-deficient mice were administered dapagliflozin (1.0 mg/kg/d) intragastrically for 6 weeks.

Mesenchymal stem cell-based therapy for radiation-induced lung injury.

Since radiotherapy is widely used in managing thoracic tumors, physicians have begun to realize that radiation-induced lung injury (RILI) seriously limits the effects of radiotherapy. Unfortunately, there are still no effective methods for controlling RILI. Over the last few decades numerous studies have reported the beneficial effects of mesenchymal stem cells (MSCs) on tissue repair and regeneration.

Overexpression of truncated AIF regulated by Egr1 promoter radiation-induced apoptosis on MCF-7 cells.

It has been demonstrated that gene-radiotherapy can improve the radiotherapy by selectively increasing cells' response to ionizing radiation. Apoptosis-inducing factor (AIF) is a mitochondrial flavoprotein, and its C-terminal domain is responsible for the proapoptotic activity. In the present study, we overexpressed truncated AIF on MCF-7 cells by transfection of pcDNA3.

Hypoxia- and radiation-induced overexpression of Smac by an adenoviral vector and its effects on cell cycle and apoptosis in MDA-MB-231 human breast cancer cells.

A conditionally replicative adenoviral (CRAd) vector, designated as CRAd.pEgr-1-Smac, that promotes the overexpression of second mitochondria-derived activator of caspase (Smac) when stimulated by hypoxia and radiation was constructed. MDA-MB-231 cells were transfected with CRAd.

Involvement of endoplasmic reticulum stress in apoptosis of testicular cells induced by low-dose radiation.

The study examined the role of endoplasmic reticulum stress (ERS) and signaling pathways of inositol-requiring enzyme-1 (IRE1), RNA-activated protein kinase-like ER kinase (PERK) and activating transcription factor-6 (ATF6) in apoptosis of mouse testicular cells treated with low-dose radiation (LDR). In the dose-dependent experiment, the mice were treated with whole-body X-ray irradiation at different doses (25, 50, 75, 100 or 200 mGy) and sacrificed 12 h later. In the time-dependent experiment, the mice were exposed to 75 mGy X-ray irradiation and killed at different time points (3, 6, 12, 18 or 24 h).

[Low-dose radiation induces endoplasmic reticulum stress and activates PERK-CHOP signaling pathway in mouse testicular cells].

Objective: To explore the correlation of low-dose radiation with endoplasmic reticulum stress and the activation of the PERK-CHOP signaling pathway in mouse testicular cells.

Methods: Healthy Kunming mice were randomly assigned to time-effect (0, 3, 6, 12 and 24 h of irradiation at 75 mGy) and dose-effect (12 h of irradiation at 0, 50, 75, 100 and 200 mGy) groups. The contents of H202 and MDA were measured by colorimetry with the agent kits, the expressions of GRP78, PERK and CHOP mRNA detected by quantitative RT-PCR, and the levels of GRP7B, PERK, phosphorylated PERK (pho-PERK) and CHOP proteins determined by Western blotting and image analysis.

Enhanced effects of TRAIL-endostatin-based double-gene-radiotherapy on suppressing growth, promoting apoptosis and inducing cell cycle arrest in vascular endothelial cells.

This study examined the effects of TRAIL-endostatin-based gene-radiotherapy on cellular growth, apoptosis and cell cycle progression in human vascular endothelial cells ECV304 in vitro. The expression of TRAIL and endostatin protein in ECV304 cells was detected by ELISA after the transfection of recombinant plasmid pshuttle-Egr1-shTRAIL-shES and X-ray irradiation. Then MTT assay was used for determining the cellular proliferation, and flow cytometry (FCM) plus Annexin V and propidium iodide (PI) double-staining or PI single-staining were employed for the detection of apoptosis and cell cycle progression.

Increased levels of p53 and PARP-1 in EL-4 cells probably related with the immune adaptive response induced by low dose ionizing radiation in vitro.

Objective: This paper is to explore the DNA repair mechanism of immune adaptive response (AR) induced by low dose radiation (LDR), the changes of mRNA levels and protein expressions of p53, ATM, DNA-PK catalytic subunit (DNA-PKcs) and PARP-1 genes in the LDR-induced AR in EL-4 cells.

Methods: The apoptosis and cell cycle progression of EL-4 cells were detected by flow cytometry in 12 h after the cells received the pre-exposure of 0.075 Gy X-rays (inductive dose, D1) and the succeeding high dose irradiation (challenge dose, D2; 1.

Inhibition of human and rat 3beta-hydroxysteroid dehydrogenase and 17beta-hydroxysteroid dehydrogenase 3 activities by perfluoroalkylated substances.

Perfluoroalkylated substances (PFASs) including perfluorooctane acid (PFOA) and perfluorooctane sulfonate (PFOS) have been classified as persistent organic pollutants and are known to cause reduced testosterone production in human males. The objective of the present study was to compare the potencies of five different PFASs including PFOA, PFOS, potassium perfluorooctane sulfonate (PFOSK), potassium perfluorohexane sulfonate (PFHxSK) and potassium perfluorobutane sulfonate (PFBSK) in the inhibition of 3beta-hydroxysteroid dehydrogenase (3beta-HSD) and 17beta-hydroxysteroid dehydrogenase 3 (17beta-HSD3) activities in the human and rat testes. Human and rat microsomal enzymes were exposed to various PFASs.

Anti-tumor effect of 125I-UdR in combination with Egr-1 promoter-based IFNγ gene therapy in vivo.

Although (125)I-UdR treatment of malignant tumors in animal models and patients has achieved a certain effect, the short half-life of (125)I-UdR in vivo and its cellular uptake only in S phase of the cell cycle are limiting factors with regard to tumor eradication, and therefore its combination with other applications is a promising strategy in cancer therapy. In this study, we show that (125)I-UdR radionuclide therapy in combination with Egr-1 promoter-based IFNγ gene therapy is more effective than (125)I-UdR therapy alone in suppressing tumor growth and extending survival duration in mice bearing H22 hepatomas. Combined therapy could significantly inhibit cell proliferation and tumor angiogenesis, induce apoptosis and enhance cytotoxic activities of splenic CTL of the mice.

Repetitive exposures to low-dose X-rays attenuate testicular apoptotic cell death in streptozotocin-induced diabetes rats.

To define whether repetitive exposures to low-dose radiation (LDR) can attenuate diabetes-induced testicular cell death, Type 1 diabetic rats were produced by single injection of streptozotocin (STZ). Once hyperglycemia was diagnosed, diabetic rats were treated with and without LDR (25 and 50 mGy X-rays) daily for 4 weeks. Eight and 12 weeks after diabetes onset, testicular apoptotic cell death was examined by flow cytometry with Annexin V/PI staining, Western blotting assay for caspase-3 cleavage, and TUNEL staining for localization of apoptotic cells.

Effect of 2-TeCD on the expression of adhesion molecules in human umbilical vein endothelial cells under the stimulation of tumor necrosis factor-alpha.

Adhesion molecules play an important role in the pathogenesis of atherogenesis. They are expressed on endothelial cells surface in response to various inflammatory stimuli. In this paper, we examined the effect of 2-tellurium-bridged beta-cyclodextrin (2-TeCD), a GPx mimic, on the expression of adhesion molecules in human umbilical vein endothelial cells (HUVECs) under tumor necrosis factor-alpha (TNF-alpha) stimulation.

Effects of corticosterone, cAMP, cGMP, Ca2+, and protein kinase C on apoptosis of mouse thymocytes induced by X-ray irradiation.

Objective: To observe the effects of signal factors of corticosterone (CS), cAMP, cGMP, Ca2+ andprotein kinase C (PKC) on lymphocyte apoptosis in mouse thymus induced by X-rays of 4 Gy in vitro.

Methods: The DNA lytic rate for thymocytes was measured by fluorospectrophotometry.

Results: The DNA lyric rate for thymocytes 4-8 hours after irradiation with 2-8 Gy was significantly higher than that in the control (P<0.

Apoptotic cell death induced by low-dose radiation in male germ cells: hormesis and adaptation.

Biological effects of low-dose radiation (LDR) in somatic cells have captured the interest of radiobiologists for the last two decades. Apoptosis of germ cells is required for normal spermatogenesis and often occurs through highly conserved events, including the transfer of vital cellular materials to the growing gametes following death of neighboring cells. Apoptosis of germ cells also functions in diverse processes, including removal of abnormal or superfluous cells at specific checkpoints, establishment of caste differentiation, and individualization of gametes.

The macrophage heterogeneity: difference between mouse peritoneal exudate and splenic F4/80+ macrophages.

Macrophages isolated from various tissues manifest differences in cell shape, the expression of surface markers, as well as metabolic and functional activities. However, the heterogeneity of macrophages expressing the same marker in different tissues has not been fully addressed. In the present study, mouse F4/80+ peritoneal exudate macrophages (PEMs) and splenic macrophages (SPMs) appeared similar in most respects.

Toll-like receptors and graft rejection.

Innate immunity plays a role in fighting against invading microorganisms. Emerging evidence suggests that in addition to responding to pathogen-associated molecular patterns of microorganisms, Toll-like receptors (TLRs) can be activated by endogenous ligands expressed by mammalian cells. Clinical and laboratory studies have shown that TLRs may participate in organ graft rejection and transplant immune tolerance, which are briefly reviewed in the present manuscript.

Effect of low-level radiation on the death of male germ cells.

Hormetic and adaptive responses induced by low-level radiation in hematopoietic and immune systems have been observed, as shown by stimulatory effects on cell growth and resistance to subsequent radiation-induced cytogenetic damage. However, in terms of cell death by apoptosis, the effects of low-level radiation are controversial: Some studies showed decreased apoptosis in response to low-level radiation while others showed increased apoptosis. This controversy may be related to the radiation doses or dose rates and also, more importantly, to the cell types.

[Changes of cycle and apoptosis of spermatogenic cells and antioxidant capacity in male rats with diabetes mellitus].

Objective: To explore the changes of cycle and apoptosis of spermatogenic cells and antioxidant capacity of the serum and testis in male rats with diabetes mellitus.

Methods: Thirty male rats were divided into two groups, 10 for normal control and 20 for the diabetes group. The rats were injected intraperitoneally with streptozocin (TZ) to develop diabetes, and 12 weeks later, their survival rate and testis weight were recorded.

[Diabetic damage to male reproduction and its mechanism].

Diabetes is a metabolic disease caused by complicated factors, and its damage to the male reproductive system is threatening men's health. This article reviews the pathophysiological changes in the diabetes-damaged male reproductive system and the mechanism of these changes. Oxidative stress induced by hyperglycemia plays an important role in working damage to the reproductive system of diabetic males, for which some anti-oxidative substances may prove to be an effective cure.

Ability of luteinizing hormone releasing hormone-Pseudomonas aeruginosa exotoxin 40 binding to LHRH receptor on human liver cancer cells.

Aim: To explore the ability of recombinant toxin luteinizing hormone releasing hormone-Pseudomonas aeruginosa exotoxin 40 (LHRH-PE40) and LHRH binding to LHRH receptor (LHRHR) on the membrane surface of human liver cancer HEPG cells.

Methods: LHRH was labeled by using (125)I with enzymatic reaction. The affinity and receptor volume of LHRH-PE40 and LHRH binding to LHRHR on the membrane surface of human liver cancer cells were measured with radioligand receptor assay.