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Long noncoding RNAs (lncRNAs) influence the transcription of gene networks in many cell types, but their role in tumor‐associated macrophages (TAMs) is still largely unknown. We found that the lncRNA ADPGK‐AS1 was substantially upregulated in artificially induced M2‐like human macrophages, macrophages exposed to lung cancer cells in vitro, and TAMs from human lung cancer tissue. ADPGK‐AS1 is partly located within mitochondria and binds to the mitochondrial ribosomal protein MRPL35. Overexpression of ADPGK‐AS1 in macrophages upregulates the tricarboxylic acid cycle and promotes mitochondrial fission, suggesting a phenotypic switch toward an M2‐like, tumor‐promoting cytokine release profile. Macrophage‐specific knockdown of ADPGK‐AS1 induces a metabolic and phenotypic switch (as judged by cytokine profile and production of reactive oxygen species) to a pro‐inflammatory tumor‐suppressive M1‐like state, inhibiting lung tumor growth in vitro in tumor cell‐macrophage cocultures, ex vivo in human tumor precision‐cut lung slices, and in vivo in mice. Silencing ADPGK‐AS1 in TAMs may thus offer a novel therapeutic strategy for lung cancer. Synopsis: Whether gene network‐controlling long noncoding RNAs also affect tumor‐associated macrophages (TAMs) is unclear. Here, the lncRNA ADPGK‐AS1 is found to be upregulated in TAMs and to drive a tumor‐promoting M2‐like phenotype associated with lung cancer growth. RNA sequencing of the artificially induced M2‐phenotype of human macrophages shows upregulated lncRNA ADPGK‐AS1 expression.ADPGK‐AS1 is expressed/located in macrophage mitochondria and interacts with the mitochondrial ribosomal protein, MRPL35.MRPL35 is highly expressed in M2‐like TAMs and is associated with poor survival in lung cancer patients.Macrophage overexpression of ADPGK‐AS1 increases mitochondrial number and fission and stimulates the tricarboxylic acid cycle, suggesting an M2‐like phenotype.TAMs with high ADPGK‐AS1 expression promote lung tumor growth, while TAMs with little expression suppress it. [ABSTRACT FROM AUTHOR]

Lung cancer classification and treatment has been revolutionized by improving our understanding of driver mutations and the introduction of tumor microenvironment (TME)-associated immune checkpoint inhibitors. Despite the significant improvement of lung cancer patient survival in response to either oncogene-targeted therapy or anticancer immunotherapy, many patients show initial or acquired resistance to these new therapies. Recent advances in genome sequencing reveal that specific driver mutations favor the development of an immunosuppressive TME phenotype, which may result in unfavorable outcomes in lung cancer patients receiving immunotherapies. Clinical studies with follow-up after immunotherapy, assessing oncogenic driver mutations and the TME immune profile, not only reveal the underlying potential molecular mechanisms in the resistant lung cancer patients but also hold the key to better treatment choices and the future of personalized medicine. In this review, we discuss the crosstalk between cancer cell genomic features and the TME to reveal the impact of genetic alterations on the TME phenotype. We also provide insights into the regulatory role of cellular TME components in defining the genetic landscape of cancer cells during tumor development. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is a disease with an inflammatory phenotype with increasing prevalence in the elderly. Expanded population of mutant blood cells carrying somatic mutations is termed clonal hematopoiesis of indeterminate potential (CHIP). The association between CHIP and COPD and its relevant effects on DNA methylation in aging are mainly unknown. Analyzing the deep-targeted amplicon sequencing from 125 COPD patients, we found enhanced incidence of CHIP mutations (~20%) with a predominance of DNMT3A CHIP-mediated hypomethylation of Phospholipase D Family Member 5 (PLD5), which in turn is positively correlated with increased levels of glycerol phosphocholine, pro-inflammatory cytokines, and deteriorating lung function. [ABSTRACT FROM AUTHOR]

Background and Objectives: Naringenin has been reported to have some promising pharmacological effects on the management of obesity and related metabolic complications including non‐alcoholic fatty liver disease (NAFLD). Therefore, the present clinical trial study was done to assess the effects of naringenin supplementation on lipid profile, aminotransferase levels, severity of steatosis, as well as probability of fibrosis in overweight/obese patients with NAFLD. Materials and Methods: This placebo‐controlled, parallel randomised, double‐blind clinical trial study was conducted on 44 eligible overweight/obese patients with NAFLD (naringenin‐treated group (n = 22), control group (n = 22)) referred to the national Iranian oil company (NIOC) Central Hospital, Tehran City, Tehran Province, Iran. Participants were randomly assigned to receive naringenin capsules (100 mg) and identical placebo capsules twice a day, before lunch and dinner, for 4 weeks. The primary outcomes were improvement of liver steatosis and NAFLD fibrosis score (NFS), and secondary outcomes included changes in levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lipid profile. Results: Naringenin consumption significantly reduced percentages of NAFLD grades (P <.001), as well as, serum levels of triglyceride (TG) (P <.001), total cholesterol (TC) (P =.01), and low‐density lipoprotein (LDL) (P =.02) and increased serum level of high‐density lipoprotein (HDL) (P =.02) compared with the control group. Even after adjusting for the confounders, the results were significant. However, there were no significant changes in AST, ALT and NFS. Conclusion: Our findings revealed that daily intake of 200 mg of naringenin for 4 weeks had beneficial effects on lipid profile and percentages of NAFLD grades as an indicator for the severity of hepatic steatosis. Although, NFS values and serum levels of aminotransferase enzymes including AST and ALT did not remarkably change. [ABSTRACT FROM AUTHOR]

Objective: Although several experimental models have suggested promising pharmacological effects of naringenin in the management of obesity and its related disorders, the effects of naringenin supplementation on cardiovascular disorders as one of the main complications of non-alcoholic fatty liver disease (NAFLD) are yet to be examined in human. Methods: In this double-blind placebocontrolled randomized clinical trial, 44 overweight/obese patients with NAFLD were equally allocated into either naringenin or placebo group for four weeks. Cardiovascular risk factors including atherogenic factors, hematological indices, obesity-related parameters, blood pressure, and heart rate were assessed pre-and post-intervention. Results: AIP value, serum non-HDL-C levels as well as total cholesterol/HDL-C, triglyceride/HDL-C, LDL-C/HDL-C, and non HDLC/HDL-C ratios were significantly reduced in the intervention group, compared to the placebo group post-intervention (P<0.05). Moreover, there was a significant reduction in BMI and visceral fat level in the intervention group when compared with the placebo group (P=0.001 and P=0.039, respectively). Furthermore, naringenin supplementation could marginally reduce systolic blood pressure (P=0.055). Mean corpuscular hemoglobin (MCH) increased significantly in the naringenin group compared to the placebo group at the endpoint (P=0.023). Supplementation with naringenin also resulted in marginally significant increase in mean corpuscular hemoglobin concentration (MCHC) when compared with the placebo group (P=0.050). There were no significant betweengroup differences for other study outcomes, postintervention. Conclusion: In conclusion, these data indicate that naringenin supplementation may be a promising treatment strategy for cardiovascular complications among NAFLD patients. However, further trials are warranted. [ABSTRACT FROM AUTHOR]