Recently, the microbiome has been gaining traction as a major player regulating various functions that correlate with many pathological conditions, including cancer. The central gut microbiota population has the capability to regulate normal inflammatory, immune, and metabolic functions, and disturbance in the balance of the normal microbiota population can subsequently induce pathological responses that closely relate with the mechanistic development and progression of cancer in various forms and sites. As a disease with major socioeconomic burden partly due to its current therapeutic options, modulating the imbalanced gut microbiota represents a novel option not only as an adjuvant therapy to relieve cancer treatment–related symptoms but also to influence cancer progression itself. In this review, we will discuss how the microbiome, specifically the gut microbiota, could affect cancer pathogenesis and what the effect of gut microbiota–targeting treatment options have on the many aspects of cancer pathologies based on the knowledge of recent years.

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Non-small-cell lung cancer (NSCLC) is a major health burden, and novel therapeutic options are needed to help solve this problem. One such option is immunotherapy, which targets immune checkpoint molecules that inhibit cancer cells, decreasing immune system activation, for example, immunotherapies target PD-1, its ligand PD-L1, and CTLA-4. There have been major advances in the development of agents that inhibit these molecules, called immune checkpoint inhibitors, and several of them are already approved for usage in NSCLC patients, especially in advanced stages. In this review, the reasons why immune checkpoint inhibitors could be beneficial and the clinical results of studies using these drugs for advanced or recurrent NSCLC patients are discussed, as is the safety profile of the drugs.

Pulmonary hypertension (PH) is a multi-etiological condition with a similar hemodynamic clinical sign and end result of right heart failure. Although its causes vary, a similar link across all the classifications is the presence of mitochondrial dysfunction. Mitochondria, as the powerhouse of the cells, hold a number of vital roles in maintaining normal cellular homeostasis, including the pulmonary vascular cells. As such, any disturbance in the normal functions of mitochondria could lead to major pathological consequences. The Warburg effect has been established as a major finding in PH conditions, but other mitochondria-related metabolic and oxidative stress factors have also been reported, making important contributions to the progression of pulmonary vascular remodeling that is commonly found in PH pathophysiology. In this review, we will discuss the role of the mitochondria in maintaining a normal vasculature, how it could be altered during pulmonary vascular remodeling, and the therapeutic options available that can treat its dysfunction.

Background Chronic obstructive pulmonary disease (COPD) is a health problem that results in death, commonly due to the development of pulmonary hypertension (PH). Here, by utilizing a mouse model of intratracheal elastase-induced emphysema that presents three different phases of COPD, we sought to observe whether budesonide/glycopyrronium/formoterol fumarate (BGF) triple therapy could prevent COPD-PH in addition to ameliorating COPD progression. Methods We utilized intratracheal elastase-induced emphysema mouse model and performed experiments in three phases illustrating COPD progression: inflammatory (1 day post-elastase), emphysema (3 weeks post-elastase) and PH (4 weeks post-elastase), while treatments of BGF and controls (vehicle, one-drug, and two-drug combinations) were started in prior to elastase instillation (inflammatory phase), at day 7 (emphysema), or at day 14 (PH phase). Phenotype analyses were performed in each phase. In vitro, A549 cells or isolated mouse lung endothelial cells (MLEC) were treated with TNFα with/without BGF treatment to analyze NFκB signaling and cytokine expression changes. Results We observed significant reductions in the proinflammatory phenotype observed in the lungs and bronchoalveolar lavage fluid (BALF) 1 day after elastase administration in mice treated with BGF compared with that in mice administered elastase alone (BALF neutrophil percentage, p = 0.0011 for PBS/Vehicle vs. PBS/Elastase, p = 0.0161 for PBS/Elastase vs. BGF). In contrast, only BGF treatment significantly ameliorated the elastase-induced emphysematous lung structure and desaturation after three weeks of elastase instillation (mean linear intercept, p = 0.0156 for PBS/Vehicle vs. PBS/Elastase, p = 0.0274 for PBS/Elastase vs. BGF). Furthermore, BGF treatment prevented COPD-PH development, as shown by improvements in the hemodynamic and histological phenotypes four weeks after elastase treatment (right ventricular systolic pressure, p = 0.0062 for PBS/Vehicle vs. PBS/Elastase, p = 0.027 for PBS/Elastase vs. BGF). Molecularly, BGF acts by inhibiting NFκB-p65 phosphorylation and subsequently decreasing the mRNA expression of proinflammatory cytokines in both alveolar epithelial and pulmonary endothelial cells. Conclusion Our results collectively showed that BGF treatment could prevent PH in addition to ameliorating COPD progression via the inhibition of inflammatory NFκB signaling.