Nanomedicine Strategies for Management of Drug Resistance in Lung Cancer

Lung cancer (LC) is one of the leading causes of cancer occurrence and mortality worldwide. Treatment of patients with advanced and metastatic LC presents a significant challenge as malignant cells use different mechanisms to resist chemotherapy. Drug resistance (DR) is a complex process that occurs due to a variety of genetic and acquired factors. Identifying the mechanisms underlying DR in LC patients and possible therapeutic alternatives for more efficient therapy is a central goal of LC research. Advances in nanotechnology resulted in the development of targeted and multifunctional nanoscale drug constructs. The possible modulation of the components of nanomedicine, their surface functionalization, and encapsulation of various active therapeutics provide promising tools to bypass crucial biological barriers. These attributes enhance the delivery of multiple therapeutic agents directly to the tumor microenvironment (TME), resulting in reversal of LC resistance to anticancer treatment. This review provides a broad framework for understanding the different molecular mechanisms of DR in lung cancer; presents novel nanomedicine therapeutics aimed to improve the efficacy of treatment of various forms of resistant LC; outlines current challenges in using nanotechnology for reversing DR; and discusses the future directions for clinical application of nanomedicine in management of LC resistance.

Synthetic Derivatives against Wild-Type and Non-Wild-Type Sporothrix brasiliensis: In Vitro and In Silico Analyses

Recently, the well-known geographically wide distribution of sporotrichosis in Brazil, combined with the difficulties of effective domestic feline treatment, has emphasized the pressing need for new therapeutic alternatives. This work considers a range of synthetic derivatives as potential antifungals against Sporothrix brasiliensis isolated from cats from the hyperendemic Brazilian region. Six S. brasiliensis isolates from the sporotrichotic lesions of itraconazole responsive or non-responsive domestic cats were studied. The minimum inhibitory concentrations (MICs) of three novel hydrazone derivatives and eleven novel quinone derivatives were determined using the broth microdilution method (M38-A2). In silico tests were also used to predict the pharmacological profile and toxicity parameters of these synthetic derivatives. MICs and MFCs ranged from 1 to >128 µg/mL. The ADMET computational analysis failed to detect toxicity while a good pharmacological predictive profile, with parameters similar to itraconazole, was obtained. Three hydrazone derivatives were particularly promising candidates as antifungal agents against itraconazole-resistant S. brasiliensis from the Brazilian hyperendemic region. Since sporotrichosis is a neglected zoonosis currently spreading in Latin America, particularly in Brazil, the present data can contribute to its future control by alternative antifungal drug design against S. brasiliensis, the most virulent and prevalent species of the hyperendemic context.

The YAP/TAZ Signaling Pathway in the Tumor Microenvironment and Carcinogenesis: Current Knowledge and Therapeutic Promises

The yes-associated protein (YAP) and the transcriptional coactivator with PDZ-binding motif (TAZ) are transcriptional coactivators, members of the Hippo signaling pathway, which play a critical role in cell growth regulation, embryonic development, regeneration, proliferation, and cancer origin and progression. The mechanism involves the nuclear binding of the un-phosphorylated YAP/TAZ complex to release the transcriptional enhanced associate domain (TEAD) from its repressors. The active ternary complex is responsible for the aforementioned biological effects. Overexpression of YAP/TAZ has been reported in cancer stem cells and tumor resistance. The resistance involves chemotherapy, targeted therapy, and immunotherapy. This review provides an overview of YAP/TAZ pathways’ role in carcinogenesis and tumor microenvironment. Potential therapeutic alternatives are also discussed.

Pathophysiology of Acute Respiratory Failure by CoV-2 Infection: Role of Oxidative Stress, Endothelial Dysfunction and Obesity

Coronavirus disease 2019 (COVID-19) due to CoV-2 (coronavirus type 2) virus possess a particular risk of developing acute respiratory distress syndrome (ARDS) or SARS (severe acute respiratory syndrome coronavirus 2)-CoV2 in people with pre-existing conditions related to endothelial dysfunction and increased pro-inflammatory and pro-oxidant state. In between these conditions, chronic systemic inflammation related to obese patients is associated with the development of atherosclerosis, type 2 diabetes, and hypertension, comorbidities that adversely affect the clinical outcome in critical patients with COVID-19. Obesity affects up to 40% of the general population in the USA and more than 30% of the adult population in Chile. Until April 2021, 1,019,478 people have been infected, with 23,524 deaths. Given the coexistence of this worldwide obesity epidemic, COVID-19 negative outcomes are seriously enhanced in the current scenario. On the other hand, obesity is characterized by endothelial dysfunction observed in different vascular beds, an alteration which can be associated with impaired vasodilation, oxidative stress, and inflammatory events. Emerging evidence shows that obesity-related conditions such as endothelial dysfunction are associated with detrimental outcomes for COVID-19 evolution, especially if the patient derives to Intensive Care Units (ICU). This implies the need to understand the pathophysiology of the infection in the obese population, in order to propose therapeutic alternatives and public health policies, especially if the virus remains in the population. In this review, we summarize evidence about the pathogeny of Cov-2 infection in obese individuals and discuss how obesity-associated inflammatory and prooxidant status increase the severity of COVID-19.

ROLE OF MANUAL THERAPY AND MASSAGE IN THE TREATMENT OF FIBROMYALGIA: TESTING THE HYPOTHESIS

Fibromyalgia syndrome (FMS) is a chronic rheumatic disease in which pain is predominant and accompanied by fatigue, anxiety, depression, sleep disturbance and cognitive dysfunction. Although there are numerous pharmacological and non-pharmacological therapeutic alternatives, symptom control is frequently problematic. Manual therapy covers manipulating soft tissue and various joints using the hands. It is organized by mapping of soft tissue structures with rhythmically applied pressure to improve physical function, facilitate daily activities, promote rehabilitation procedures and decrease pain. Massage is generally accepted as an essential component of manual therapy. Stretching and mobilizations are also part of manual therapy. Although numerous beneficial effects of manual therapy and massage on the musculoskeletal system and pain have been proven, the data in FMS patients studies are inconclusive. We hypothesize that manual therapy and massage are beneficial therapeutic options for the control of symptoms of FMS patients. Furthermore, these strategies can be employed in conjunction with well-established and high-evidence therapeutic procedures. Future research should focus on establishing standardized protocols for manual therapy and massage, which is one of the major limitations. To ensure a high level of evidence, research studies with large sample sizes, long follow-up periods and methodologically complete are needed.

Radiosurgery for brain oligometastases in lung cancer

INTRODUCTION Brain metastases are a common problem in oncology patients, especially in lung cancer. The usual treatment for cerebral oligometastases is whole brain radiation therapy. Given the persistent poor prognosis of this disease, other therapeutic alternatives such as stereotactic radiosurgery have been considered. However, there is no clarity regarding the effectiveness of its addition. METHODS We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS We identified 17 systematic reviews including seven studies overall, of which four were randomized trials. All trials assessed patients with brain oligometastases, but none of them included exclusively lung cancer population. We concluded that it is not possible to clearly establish whether radiosurgery decreases neurological functionality, cognitive impairment, mortality or serious adverse effects, as the certainty of the existing evidence has been assessed as very low.

Antitumor Effects of Natural Compounds Derived from Allium sativum on Neuroblastoma: An Overview

Garlic (Allium sativum) has been used in alternative medicine to treat several diseases, such as cardiovascular and neurodegenerative diseases, cancer, and hepatic diseases. Several publications have highlighted other features of garlic, including its antibacterial, antioxidative, antihypertensive, and antithrombotic properties. The properties of garlic result from the combination of natural compounds that act synergistically and cause different effects. Some garlic-derived compounds have been studied for the treatment of several types of cancer; however, reports on the effects of garlic on neuroblastoma are scarce. Neuroblastoma is a prevalent childhood tumor for which the search for therapeutic alternatives to improve treatment without affecting the patients’ quality of life continues. Garlic-derived compounds hold potential for the treatment of this type of cancer. A review of articles published to date on some garlic compounds and their effect on neuroblastoma was undertaken to comprehend the possible therapeutic role of these compounds. This review aimed to analyze the impact of some garlic compounds on cells derived from neuroblastoma.

ACP-MHCNN: an accurate multi-headed deep-convolutional neural network to predict anticancer peptides

Although advancing the therapeutic alternatives for treating deadly cancers has gained much attention globally, still the primary methods such as chemotherapy have significant downsides and low specificity. Most recently, Anticancer peptides (ACPs) have emerged as a potential alternative to therapeutic alternatives with much fewer negative side-effects. However, the identification of ACPs through wet-lab experiments is expensive and time-consuming. Hence, computational methods have emerged as viable alternatives. During the past few years, several computational ACP identification techniques using hand-engineered features have been proposed to solve this problem. In this study, we propose a new multi headed deep convolutional neural network model called ACP-MHCNN, for extracting and combining discriminative features from different information sources in an interactive way. Our model extracts sequence, physicochemical, and evolutionary based features for ACP identification using different numerical peptide representations while restraining parameter overhead. It is evident through rigorous experiments using cross-validation and independent-dataset that ACP-MHCNN outperforms other models for anticancer peptide identification by a substantial margin on our employed benchmarks. ACP-MHCNN outperforms state-of-the-art model by 6.3%, 8.6%, 3.7%, 4.0%, and 0.20 in terms of accuracy, sensitivity, specificity, precision, and MCC respectively. ACP-MHCNN and its relevant codes and datasets are publicly available at: https://github.com/mrzResearchArena/Anticancer-Peptides-CNN. ACP-MHCNN is also publicly available as an online predictor at: https://anticancer.pythonanywhere.com/.

Bioactive cationic peptides as potential agents for breast cancer treatment

Breast cancer continues to affect millions of women worldwide, and the number of new cases dramatically increases every year. The physiological causes behind the disease are still not fully understood. One in every 100 cases can occur in men, and although the frequency is lower than among women, men tend to have a worse prognosis of the disease. Various therapeutic alternatives to combat the disease are available. These depend on the type and progress of the disease, and include chemotherapy, radiotherapy, surgery, and cancer immunotherapy. However, there are several well-reported side effects of these treatments that have a significant impact on life quality, and patients either relapse or are refractory to treatment. This makes it necessary to develop new therapeutic strategies. One promising initiative are bioactive peptides, which have emerged in recent years as a family of compounds with an enormous number of clinical applications due to their broad spectrum of activity. They are widely distributed in several organisms as part of their immune system. The antitumoral activity of these peptides lies in a nonspecific mechanism of action associated with their interaction with cancer cell membranes, inducing, through several routes, bilayer destabilization and cell death. This review provides an overview of the literature on the evaluation of cationic peptides as potential agents against breast cancer under different study phases. First, physicochemical characteristics such as the primary structure and charge are presented. Secondly, information about dosage, the experimental model used, and the mechanism of action proposed for the peptides are discussed.