CMTM4 inhibits gastric tumorigenesis and metastasis.

Background: CKLF-like MARVEL transmembrane domain-containing 4 (CMTM4) is involved in immune regulation and tumor progression; however, its role in gastric cancer (GC) remains unclear. This study explored the role and mechanism of CMTM4 in GC. Methods: Immunohistochemistry was used to analyze CMTM4 expression in human gastric biopsied cells from patients with GC (N=23) or chronic superficial gastritis (N=23). To investigate the function of CMTM4 in GC cells, the gene CMTM4 was knocked down and overexpressed in human gastric adenocarcinoma cell line AGS. The gene CMTM4 was overexpressed in AGS cells and human gastric cell line SGC7901. Cell Counting Kit 8 (CCK-8) and cell clonogenic assays were used to analyze the proliferation of the GC cells. Flow cytometry was used to analyze the effects of CMTM4 on apoptosis and the cell cycle. Wound healing and transwell assays were used to analyze the migration and invasion of the gastric cells, respectively. The mechanism of CMTM4 in GC cells was explored using the tandem mass tags (TMTs) proteome and verified by western blot analysis. Results: CMTM4 expression was more downregulated in the human GC tissues than the gastritis tissues. CMTM4 overexpression significantly inhibited the proliferation, migration, and invasion of the GC cells, whereas CMTM4 knockdown enhanced gastric cell proliferation (P>0.05), migration (P>0.05), and invasion (P>0.05). Flow cytometry showed that CMTM4 promoted apoptosis and resulted in G1/S arrest in the GC cells. In addition, the proteome and western blot results showed that STAT1 was significantly upregulated, and the STAT1 signaling pathways were enriched in the GC cells overexpressing CMTM4. Conclusions: Our results suggest that CMTM4 plays a tumor-suppressive role in GC and may affect the growth, migration, and invasion of GC cells through the STAT1 signaling pathway. CMTM4 might have potential value as a prognosis marker and potential therapeutic target for GC therapy.

Personalized medicine: Clinical oncology on molecular view of treatment.

Cancer, the second leading global cause of death, impacts both physically and emotionally. Conventional treatments such as surgeries, chemotherapy, and radiotherapy have adverse effects, driving the need for more precise approaches. Precision medicine enables more targeted treatments. Genetic mapping, alongside other molecular biology approaches, identifies specific genes, contributing to accurate prognoses. The review addresses, in clinical use, a molecular perspective on treatment. Biomarkers like alpha-fetoprotein, beta-human chorionic gonadotropin, 5-hydroxyindoleacetic acid, programmed death-1, and cytotoxic T lymphocyte-associated protein 4 are explored, providing valuable information. Bioinformatics, with an emphasis on artificial intelligence, revolutionizes the analysis of biological data, offering more accurate diagnoses. Techniques like liquid biopsy are emphasized for early detection. Precision medicine guides therapeutic strategies based on the molecular characteristics of the tumor, as evidenced in the molecular subtypes of breast cancer. Classifications allow personalized treatments, highlighting the role of trastuzumab and endocrine therapies. Despite the benefits, challenges persist, including high costs, tumor heterogeneity, and ethical issues. Overcoming obstacles requires collaboration, ensuring that advances in molecular biology translate into accessible benefits for all.

Long chikungunya? An overview to immunopathology of persistent arthralgia.

Chikungunya fever (CF) is caused by an arbovirus whose manifestations are extremely diverse, and it has evolved with significant severity in recent years. The clinical signs triggered by the Chikungunya virus are similar to those of other arboviruses. Generally, fever starts abruptly and reaches high levels, followed by severe polyarthralgia and myalgia, as well as an erythematous or petechial maculopapular rash, varying in severity and extent. Around 40% to 60% of affected individuals report persistent arthralgia, which can last from months to years. The symptoms of CF mainly represent the tissue tropism of the virus rather than the immunopathogenesis triggered by the host's immune system. The main mechanisms associated with arthralgia have been linked to an increase in T helper type 17 cells and a consequent increase in receptor activator of nuclear factor kappa-Β ligand and bone resorption. This review suggests that persistent arthralgia results from the presence of viral antigens post-infection and the constant activation of signaling lymphocytic activation molecule family member 7 in synovial macrophages, leading to local infiltration of CD4+ T cells, which sustains the inflammatory process in the joints through the secretion of pro-inflammatory cytokines. The term "long chikungunya" was used in this review to refer to persistent arthralgia since, due to its manifestation over long periods after the end of the viral infection, this clinical condition seems to be characterized more as a sequel than as a symptom, given that there is no active infection involved.

In silico prospective analysis of the medicinal plants activity on the CagA oncoprotein from Helicobacter pylori.

BACKGROUND: Colonization with Helicobacter pylori (H. pylori) has a strong correlation with gastric cancer, and the virulence factor CagA is implicated in carcinogenesis. Studies have been conducted using medicinal plants with the aim of eliminating the pathogen; however, the possibility of blocking H. pylori-induced cell differentiation to prevent the onset and/or progression of tumors has not been addressed. This type of study is expensive and time-consuming, requiring in vitro and/or in vivo tests, which can be solved using bioinformatics. Therefore, prospective computational analyses were conducted to assess the feasibility of interaction between phenolic compounds from medicinal plants and the CagA oncoprotein. AIM: To perform a computational prospecting of the interactions between phenolic compounds from medicinal plants and the CagA oncoprotein of H. pylori. METHODS: In this in silico study, the structures of the phenolic compounds (ligands) kaempferol, myricetin, quercetin, ponciretin (flavonoids), and chlorogenic acid (phenolic acid) were selected from the PubChem database. These phenolic compounds were chosen based on previous studies that suggested medicinal plants as non-drug treatments to eliminate H. pylori infection. The three-dimensional structure model of the CagA oncoprotein of H. pylori (receptor) was obtained through molecular modeling using computational tools from the I-Tasser platform, employing the threading methodology. The primary sequence of CagA was sourced from GenBank (BAK52797.1). A screening was conducted to identify binding sites in the structure of the CagA oncoprotein that could potentially interact with the ligands, utilizing the GRaSP online platform. Both the ligands and receptor were prepared for molecular docking using AutoDock Tools 4 (ADT) software, and the simulations were carried out using a combination of ADT and AutoDock Vina v.1.2.0 software. Two sets of simulations were performed: One involving the central region of CagA with phenolic compounds, and another involving the carboxy-terminus region of CagA with phenolic compounds. The receptor-ligand complexes were then analyzed using PyMol and BIOVIA Discovery Studio software. RESULTS: The structure model obtained for the CagA oncoprotein exhibited high quality (C-score = 0.09) and was validated using parameters from the MolProbity platform. The GRaSP online platform identified 24 residues (phenylalanine and leucine) as potential binding sites on the CagA oncoprotein. Molecular docking simulations were conducted with the three-dimensional model of the CagA oncoprotein. No complexes were observed in the simulations between the carboxy-terminus region of CagA and the phenolic compounds; however, all phenolic compounds interacted with the central region of the oncoprotein. Phenolic compounds and CagA exhibited significant affinity energy (-7.9 to -9.1 kcal/mol): CagA/kaempferol formed 28 chemical bonds, CagA/myricetin formed 18 chemical bonds, CagA/quercetin formed 16 chemical bonds, CagA/ponciretin formed 13 chemical bonds, and CagA/chlorogenic acid formed 17 chemical bonds. Although none of the phenolic compounds directly bound to the amino acid residues of the K-Xn-R-X-R membrane binding motif, all of them bound to residues, mostly positively or negatively charged, located near this region. CONCLUSION: In silico, the tested phenolic compounds formed stable complexes with CagA. Therefore, they could be tested in vitro and/or in vivo to validate the findings, and to assess interference in CagA/cellular target interactions and in the oncogenic differentiation of gastric cells.

New avenues for the treatment of immunotherapy-resistant pancreatic cancer.

Pancreatic cancer (PC) is characterized by its extremely aggressive nature and ranks 14th in the number of new cancer cases worldwide. However, due to its complexity, it ranks 7th in the list of the most lethal cancers worldwide. The pathogenesis of PC involves several complex processes, including familial genetic factors associated with risk factors such as obesity, diabetes mellitus, chronic pancreatitis, and smoking. Mutations in genes such as KRAS, TP53, and SMAD4 are linked to the appearance of malignant cells that generate pancreatic lesions and, consequently, cancer. In this context, some therapies are used for PC, one of which is immunotherapy, which is extremely promising in various other types of cancer but has shown little response in the treatment of PC due to various resistance mechanisms that contribute to a drop in immunotherapy efficiency. It is therefore clear that the tumor microenvironment (TME) has a huge impact on the resistance process, since cellular and non-cellular elements create an immunosuppressive environment, characterized by a dense desmoplastic stroma with cancer-associated fibroblasts, pancreatic stellate cells, extracellular matrix, and immunosuppressive cells. Linked to this are genetic mutations in TP53 and immunosuppressive factors that act on T cells, resulting in a shortage of CD8+ T cells and limited expression of activation markers such as interferon-gamma. In this way, finding new strategies that make it possible to manipulate resistance mechanisms is necessary. Thus, techniques such as the use of TME modulators that block receptors and stromal molecules that generate resistance, the use of genetic manipulation in specific regions, such as microRNAs, the modulation of extrinsic and intrinsic factors associated with T cells, and, above all, therapeutic models that combine these modulation techniques constitute the promising future of PC therapy. Thus, this study aims to elucidate the main mechanisms of resistance to immunotherapy in PC and new ways of manipulating this process, resulting in a more efficient therapy for cancer patients and, consequently, a reduction in the lethality of this aggressive cancer.

Temporal pattern of humoral immune response in mild cases of COVID-19.

BACKGROUND: Understanding the humoral response pattern of coronavirus disease 2019 (COVID-19) is one of the essential factors to better characterize the immune memory of patients, which allows understanding the temporality of reinfection, provides answers about the efficacy and durability of protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and consequently helps in global public health and vaccination strategy. Among the patients who became infected with SARS-CoV-2, the majority who did not progress to death were those who developed the mild COVID-19, so understanding the pattern and temporality of the antibody response of these patients is certainly relevant. AIM: To investigate the temporal pattern of humoral response of specific immunoglobulin G (IgG) in mild cases of COVID-19. METHODS: Blood samples from 191 COVID-19 real-time reverse transcriptase-polymerase chain reaction (RT-qPCR)-positive volunteers from the municipality of Toledo/ Paraná/Brazil, underwent two distinct serological tests, enzyme-linked immunosorbent assay, and detection of anti-nucleocapsid IgG. Blood samples and clinicoepidemiological data of the volunteers were collected between November 2020 and February 2021. All assays were performed in duplicate and the manufacturers' recommendations were strictly followed. The data were statistically analyzed using multiple logistic regression; the variables were selected by applying the P < 0.05 criterion. RESULTS: Serological tests to detect specific IgG were performed on serum samples from volunteers who were diagnosed as being positive by RT-qPCR for COVID-19 or had disease onset in the time interval from less than 1 mo to 7 mo. The time periods when the highest number of participants with detectable IgG was observed were 1, 2 and 3 mo. It was observed that 9.42% of participants no longer had detectable IgG antibodies 1 mo only after being infected with SARS-CoV-2 and 1.57% were also IgG negative at less than 1 mo. At 5 mo, 3.14% of volunteers were IgG negative, and at 6 or 7 mo, 1 volunteer (0.52%) had no detectable IgG. During the period between diagnosis by RT-qPCR/symptoms onset and the date of collection for the study, no statistical significance was observed for any association analyzed. Moreover, considering the age category between 31 and 59 years as the exposed group, the P value was 0.11 for the category 31 to 59 years and 0.32 for the category 60 years or older, showing that in both age categories there was no association between the pair of variables analyzed. Regarding chronic disease, the exposure group consisted of the participants without any comorbidity, so the P value of 0.07 for the category of those with at least one chronic disease showed no association between the two variables. CONCLUSION: A temporal pattern of IgG response was not observed, but it is suggested that immunological memory is weak and there is no association between IgG production and age or chronic disease in mild COVID-19.

Benefits of high-intensity interval training compared to continuous training to reduce apoptotic markers in female rats with cisplatin nephrotoxicity - possible modulatory role of IL-11.

Apoptotic signaling pathways are involved in acute kidney injury (AKI) induced by the antineoplastic drug cisplatin (Cis). Mechanical stress is known to increase interleukin (IL) -11, a pleiotropic cytokine with antiapoptotic and antinecrotic effects. We compared the impact of high-intensity interval training (HIIT) with low-intensity continuous training (LICT) and moderate-intensity continuous training (MICT) on renal levels of IL-11 and the expression of apoptotic markers in female rats with nephrotoxicity induced by Cis. For that, the animals were divided into five groups (n = 7): control and sedentary (C + S); Cis and sedentary (Cis + S); Cis and LICT (Cis + LICT); Cis and MICT (Cis + MICT) and Cis and HIIT (Cis + HIIT). At the end of 8 weeks of treadmill running, the rats received a single injection of Cis (5 mg/kg), and 7 days later they were euthanized. Serum and kidney samples were collected to assess the blood urea nitrogen (BUN), gene expression of TNF receptor 1 (TNFR1) and 2 (TNFR2), caspase-3, (p38) MAPK (MAPK14), p53, Bax, Bak, Bcl-2, and Bcl-xL, renal levels of IL-11, IL-8, and p53, and immunolocalization of cleaved caspase-3, Bax, Bcl-2, and (p38) MAPK in renal tissue. Our data indicate that all trained groups showed a significant intensity-dependent increase in renal levels of IL-11 associated with reduced local expression of proapoptotic and increased antiapoptotic markers, but these effects were more pronounced with HIIT. So, HIIT appears to provide superior renoprotection than traditional continuous training by modulating apoptotic signaling pathways, and this effect can be related to the increase in renal levels of IL-11.

COVID-19 liver and gastroenterology findings: An in silico analysis of SARS-CoV-2 interactions with liver molecules.

BACKGROUND: Coronavirus disease 19 (COVID-19) has not only been shown to affect the respiratory system, but has also demonstrated variable clinical presentations including gastrointestinal tract disorders. In addition, abnormalities in liver enzymes have been reported indicating hepatic injury. It is known that severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) might infect cells via the viral receptor angiotensin-converting enzyme 2 (ACE2) which is expressed in several organs including the liver. The viral Spike glycoprotein binds to ACE2 and must be cleaved by Furin and Type 2 Serine Protease to enter the cells. After that, the Akt/mTOR signaling pathway is activated and several COVID-19 changes are triggered. AIM: To analyze liver and gastrointestinal symptoms and cell signaling pathways triggered by SARS-CoV-2 infection due to virus-liver interactions in silico. METHODS: In this in silico study, the three-dimensional structures of the Akt, mTORC1 and Furin (receptors) were selected from the Protein Data Bank (PDB) and the structures of inhibitors (ligands) MK-2206, CC-223 and Naphthofluorescein were selected from PubChem and ZINC databases. Ligand files were downloaded as 2D structures and converted to optimized 3D structures using ViewerLite 4.2 software. Marvin Sketch® software was used to calculate prediction of the protonated form of inhibitors in a physiological environment (pH 7.4). AutoDock Tools (ADT) software was used to calculate and delimit the Grid box used in the molecular docking of each structure selected in the PDB. In addition, protonated ligands were prepared for molecular docking using ADT software. Molecular docking was performed using ADT software tools connected to Vina software. Analysis of the amino acid residues involved in ligand interactions, as well as ligand twists, the atoms involved in interactions, bond type and strength of interactions were performed using PyMol® and Discovery Studio® (BIOVIA) software. RESULTS: Molecular docking analysis showed that the mTORC1/CC-223 complex had affinity energy between the receptor and ligand of -7.7 kcal/moL with interactions ranging from 2.7 to 4.99 Å. There were four significant chemical bonds which involved two of five polypeptide chains that formed the FKBP12-Rapamycin-Binding (FRB) domain. The strongest was a hydrogen bond, the only polar interaction, and Van der Waals interactions shown to be present in 12 residues of mTORC1's FRB domain. With regard to the Akt/MK-2206 complex there were three Van der Waals interactions and 12 chemical bonds in which seven residues of Akt were involved with all five rings of the MK-2206 structure. In this way, both ASP 388 and GLN 391 bind to the same MK-2206 ring, the smaller one. However, LYS 386 had four chemical bonds with the inhibitor, one with each structure ring, while LYS 387 binds two distinct rings. One of the MK-2206 inhibitor's rings which binds to LYS 387 also binds simultaneously to ILE 367 and LEU 385 residues, and the fifth ring of the structure was involved in a bond with the ALA 382 residue. The hydrogen bonds were the shortest bonds in the complex (2.61 and 3.08 Å) and all interactions had an affinity energy of -8.8 kcal/moL. The affinity energy in the Furin/Naphhofluorescein complex was -9.8 kcal/moL and involved six interactions ranging from 2.57 to 4.98 Å. Among them, two were polar and the others were non-polar, in addition to twelve more Van der Waals interactions. Two distinct hydrogen bonds were formed between Furin and its inhibitor involving GLN 388 and ALA 532 residues. ALA 532 also binds to two distinct rings of Naphthofluorescein, while TRP 531 residue has two simultaneous bonds with the inhibitor. CONCLUSION: Liver infection and signaling pathways altered by SARS-CoV-2 can be modulated by inhibitors that demonstrate significant interaction affinity with human proteins, which could prevent the development of infection and symptoms.

Molecular and serology methods in the diagnosis of COVID-19: An overview.

Coronavirus disease-19 (COVID-19) has become a pandemic, being a global health concern since December 2019 when the first cases were reported. Severe acute respiratory syndrome coronavirus 2, the COVID-19 causal agent, is a ß-coronavirus that has on its surface the spike protein, which helps in its virulence and pathogenicity towards the host. Thus, effective and applicable diagnostic methods to this disease come as an important tool for the management of the patients. The use of the molecular technique PCR, which allows the detection of the viral RNA through nasopharyngeal swabs, is considered the gold standard test for the diagnosis of COVID-19. Moreover, serological methods, such as enzyme-linked immunosorbent assays and rapid tests, are able to detect severe acute respiratory syndrome coronavirus 2-specific immunoglobulin A, immunoglobulin M, and immunoglobulin G in positive patients, being important alternative techniques for the diagnostic establishment and epidemiological surveillance. On the other hand, reverse transcription loop-mediated isothermal amplification also proved to be a useful diagnostic method for the infection, mainly because it does not require a sophisticated laboratory apparatus and has similar specificity and sensitivity to PCR. Complementarily, imaging exams provide findings of typical pneumonia, such as the ground-glass opacity radiological pattern on chest computed tomography scanning, which along with laboratory tests assist in the diagnosis of COVID-19.

From Helicobacter pylori infection to gastric cancer: Current evidence on the immune response.

Gastric cancer (GC) is the result of a multifactorial process whose main components are infection by Helicobacter pylori (H. pylori), bacterial virulence factors, host immune response and environmental factors. The development of the neoplastic microenvironment also depends on genetic and epigenetic changes in oncogenes and tumor suppressor genes, which results in deregulation of cell signaling pathways and apoptosis process. This review summarizes the main aspects of the pathogenesis of GC and the immune response involved in chronic inflammation generated by H. pylori.

Non-pharmacological management of pediatric functional abdominal pain disorders: Current evidence and future perspectives.

Functional abdominal pain disorders (FAPDs) are an important and prevalent cause of functional gastrointestinal disorders among children, encompassing the diagnoses of functional dyspepsia, irritable bowel syndrome, abdominal migraine, and the one not previously present in Rome III, functional abdominal pain not otherwise specified. In the absence of sufficiently effective and safe pharmacological treatments for this public problem, non-pharmacological therapies emerge as a viable means of treating these patients, avoiding not only possible side effects, but also unnecessary prescription, since many of the pharmacological treatments prescribed do not have good efficacy when compared to placebo. Thus, the present study provides a review of current and relevant evidence on non-pharmacological management of FAPDs, covering the most commonly indicated treatments, from cognitive behavioral therapy to meditation, acupuncture, yoga, massage, spinal manipulation, moxibustion, and physical activities. In addition, this article also analyzes the quality of publications in the area, assessing whether it is possible to state if non-pharmacological therapies are viable, safe, and sufficiently well-based for an appropriate and effective prescription of these treatments. Finally, it is possible to observe an increase not only in the number of publications on the non-pharmacological treatments for FAPDs in recent years, but also an increase in the quality of these publications. Finally, the sample selection of satisfactory age groups in these studies enables the formulation of specific guidelines for this age group, thus avoiding the need for adaptation of prescriptions initially made for adults, but for children use.

Helicobacter pylori infection: How does age influence the inflammatory pattern?

The inflammatory pattern during Helicobacter pylori (H. pylori) infection is changeable and complex. During childhood, it is possible to observe a predominantly regulatory response, evidenced by high concentrations of key cytokines for the maintenance of Treg responses such as TGF-ß1 and IL-10, in addition to high expression of the transcription factor FOXP3. On the other hand, there is a predominance of cytokines associated with the Th1 and Th17 responses among H. pylori-positive adults. In the last few years, the participation of the Th17 response in the gastric inflammation against H. pylori infection has been highlighted due to the high levels of TGF-ß1 and IL-17 found in this infectious scenario, and growing evidence has supported a close relationship between this immune response profile and unfavorable outcomes related to the infection. Moreover, this cytokine profile might play a pivotal role in the effectiveness of anti-H. pylori vaccines. It is evident that age is one of the main factors influencing the gastric inflammatory pattern during the infection with H. pylori, and understanding the immune response against the bacterium can assist in the development of alternative prophylactic and therapeutic strategies against the infection as well as in the comprehension of the pathogenesis of the outcomes related to that microorganism.

Transmission of severe acute respiratory syndrome coronavirus 2 via fecal-oral: Current knowledge.

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in more than 93 million cases and 2 million deaths in the world. SARS-CoV-2 respiratory tract infection and its main clinical manifestations such as cough and shortness of breath are well known to the scientific community. However, a growing number of studies have reported SARS-CoV-2-related gastrointestinal involvement based on clinical manifestations, such as diarrhea, nausea, vomiting, and abdominal pain as well as on the pathophysiological mechanisms associated with coronavirus disease 2019. Furthermore, current evidence suggests SARS-CoV-2 transmission via the fecal-oral route and aerosol dissemination. Moreover, studies have shown a high risk of contamination through hospital surfaces and personal fomites. Indeed, viable SARS-CoV-2 specimens can be obtained from aerosols, which raises the possibility of transmission through aerosolized viral particles from feces. Therefore, the infection by SARS-CoV-2 via fecal-oral route or aerosolized particles should be considered. In addition, a possible viral spread to sources of drinking water, sewage, and rivers as well as the possible risk of viral transmission in shared toilets become a major public health concern, especially in the least developed countries. Since authors have emphasized the presence of viral RNA and even viable SARS-CoV-2 in human feces, studies on the possible fecal-oral coronavirus disease 2019 transmission become essential to understand better the dynamics of its transmission and, then, to reinforce preventive measures against this infection, leading to a more satisfactory control of the incidence of the infection.

Relationship between Th17 immune response and cancer.

Cancer is the second leading cause of death worldwide and epidemiological projections predict growing cancer mortality rates in the next decades. Cancer has a close relationship with the immune system and, although Th17 cells are known to play roles in the immune response against microorganisms and in autoimmunity, studies have emphasized their roles in cancer pathogenesis. The Th17 immune response profile is involved in several types of cancer including urogenital, respiratory, gastrointestinal, and skin cancers. This type of immune response exerts pro and antitumor functions through several mechanisms, depending on the context of each tumor, including the protumor angiogenesis and exhaustion of T cells and the antitumor recruitment of T cells and neutrophils to the tumor microenvironment. Among other factors, the paradoxical behavior of Th17 cells in this setting has been attributed to its plasticity potential, which makes possible their conversion into other types of T cells such as Th17/Treg and Th17/Th1 cells. Interleukin (IL)-17 stands out among Th17-related cytokines since it modulates pathways and interacts with other cell profiles in the tumor microenvironment, which allow Th17 cells to prevail in tumors. Moreover, the IL-17 is able to mediate pro and antitumor processes that influence the development and progression of various cancers, being associated with variable clinical outcomes. The understanding of the relationship between the Th17 immune response and cancer as well as the singularities of carcinogenic processes in each type of tumor is crucial for the identification of new therapeutic targets.

Oncolytic virus therapy in cancer: A current review.

In view of the advancement in the understanding about the most diverse types of cancer and consequently a relentless search for a cure and increased survival rates of cancer patients, finding a therapy that is able to combat the mechanism of aggression of this disease is extremely important. Thus, oncolytic viruses (OVs) have demonstrated great benefits in the treatment of cancer because it mediates antitumor effects in several ways. Viruses can be used to infect cancer cells, especially over normal cells, to present tumor-associated antigens, to activate "danger signals" that generate a less immune-tolerant tumor microenvironment, and to serve transduction vehicles for expression of inflammatory and immunomodulatory cytokines. The success of therapies using OVs was initially demonstrated by the use of the genetically modified herpes virus, talimogene laherparepvec, for the treatment of melanoma. At this time, several OVs are being studied as a potential treatment for cancer in clinical trials. However, it is necessary to be aware of the safety and possible adverse effects of this therapy; after all, an effective treatment for cancer should promote regression, attack the tumor, and in the meantime induce minimal systemic repercussions. In this manuscript, we will present a current review of the mechanism of action of OVs, main clinical uses, updates, and future perspectives on this treatment.

Highlighting COVID-19: What the imaging exams show about the disease.

Coronavirus disease 2019 (COVID-19), a global emergency, is caused by severe acute respiratory syndrome coronavirus 2. The gold standard for its diagnosis is the reverse transcription polymerase chain reaction, but considering the high number of infected people, the low availability of this diagnostic tool in some contexts, and the limitations of the test, other tools that aid in the identification of the disease are necessary. In this scenario, imaging exams such as chest X-ray (CXR) and computed tomography (CT) have played important roles. CXR is useful for assessing disease progression because it allows the detection of extensive consolidations, besides being a fast and cheap method. On the other hand, CT is more sensitive for detecting lung changes in the early stages of the disease and is also useful for assessing disease progression. Of note, ground-glass opacities are the main COVID-19-related CT findings. Positron emission tomography combined with CT can be used to evaluate chronic and substantial damage to the lungs and other organs; however, it is an expensive test. Lung ultrasound (LUS) has been shown to be a promising technique in that context as well, being useful in the screening and monitoring of patients, disease classification, and management related to mechanical ventilation. Moreover, LUS is an inexpensive alternative available at the bedside. Finally, magnetic resonance imaging, although not usually requested, allows the detection of pulmonary, cardiovascular, and neurological abnormalities associated with COVID-19. Furthermore, it is important to consider the challenges faced in the radiology field in the adoption of control measures to prevent infection and in the follow-up of post-COVID-19 patients.

Tertiary peritonitis: A disease that should not be ignored.

Intra-abdominal infections can be classified into uncomplicated or complicated (peritonitis). Peritonitis is divided into primary, secondary, and tertiary. Tertiary peritonitis is the less common but the most severe among peritonitis stratifications, being defined as a recurrent intra-abdominal infection that occurs 48 h after a well-succeeded control of a secondary peritonitis. This disease has a complex pathogenesis that is closely related to the capacity of the peritoneal cavity to activate immunological processes. Patients who progress to persistent peritonitis are at an increased risk of developing several infectious complications such as sepsis and multiple organ failure syndrome. Moreover, tertiary peritonitis remains an important cause of hospital death mainly among patients with associated risk factors. The microbiological profile of organisms causing tertiary peritonitis is often different from that observed in other types of peritonitis. In addition, there is a high prevalence of multidrug-resistant pathogens causing this condition, and an appropriate and successful clinical management depends on an early diagnosis, which can be made easier with the use of clinical scores presenting a good prediction value during the intensive care unit admission. Complementarily, immediate therapy should be performed to control the infectious focus and to prevent new recurrences. In this sense, the treatment is based on initial antimicrobial therapy and well-performed peritoneal drainage.

Chronic myeloid leukemia-from the Philadelphia chromosome to specific target drugs: A literature review.

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm and was the first neoplastic disease associated with a well-defined genotypic anomaly - the presence of the Philadelphia chromosome. The advances in cytogenetic and molecular assays are of great importance to the diagnosis, prognosis, treatment, and monitoring of CML. The discovery of the breakpoint cluster region (BCR)-Abelson murine leukemia (ABL) 1 fusion oncogene has revolutionized the treatment of CML patients by allowing the development of targeted drugs that inhibit the tyrosine kinase activity of the BCR-ABL oncoprotein. Tyrosine kinase inhibitors (known as TKIs) are the standard therapy for CML and greatly increase the survival rates, despite adverse effects and the odds of residual disease after discontinuation of treatment. As therapeutic alternatives, the subsequent TKIs lead to faster and deeper molecular remissions; however, with the emergence of resistance to these drugs, immunotherapy appears as an alternative, which may have a cure potential in these patients. Against this background, this article aims at providing an overview on CML clinical management and a summary on the main targeted drugs available in that context.

Simultaneous circulation of zakat, dengue, and chikungunya viruses and their vertical co-transmission among Aedes aegypti.

The outbreaks caused by the Aedes aegypti-transmitted dengue virus (DENV), zakat virus (ZIKV), and chikungunya virus (CHIKV) result in a significant impact to the health systems of tropical countries. Furthermore, the occurrence of patients coinfected by at least two of these arboviruses is an aggravating factor in that scenario. On this basis, surveillance tools such as the Rapid Index Survey for Aedes aegypti (LIRAa) are used to estimate vector infestation in order to improve the prediction of human outbreaks. Ae. aegypti eggs were collected in the city of Vitória da Conquista, in Bahia State, Brazil, and subsequently hatched into larvae, which were analyzed in pools or individually for the presence of DENV, ZIKV, and CHIKV by molecular biology methods. The detection data for arboviruses were crossed with the LIRAa obtained in each region of the study city. Thirty larvae pools were analyzed, and fourteen (46.6%) of them were detected positive for DENV, ZIKV, and/or CHIKV. Among the individually analyzed larvae (n = 30), nine (30%) were positive for any of these arboviruses, and four (13.3%) were simultaneously coinfected by DENV and ZIKV. Furthermore, there was a positive correlation between the detection of circulating arboviruses and LIRAa. The simultaneous Ae. aegypti larvae infection by two different arboviruses is an unprecedented finding. This result suggests the occurrence of a vertical arboviruses co-transmission from the female mosquito to its offspring in nature. The occurrence of concomitant circulation of DENV, ZIKV, and CHIKV in Ae. aegypti from a single study region is another finding of this article. Finally, LIRAa seems to not only estimate vector infestation but also to predict circulation of arboviruses.

High-intensity interval training is more effective than continuous training to reduce inflammation markers in female rats with cisplatin nephrotoxicity.

AIMS: Cisplatin (CP) is an antineoplastic widely used in the treatment of various solid tumors, however, its clinical application is limited by nephrotoxicity. Here, we compared the impact of preconditioning with high-intensity interval training (HIIT) with continuous training of low (LIT) and moderate (MIT) intensity on innate immunity markers in female rats with CP-induced acute kidney injury. MATERIALS AND METHODS: The rats were divided into five groups (n = 7): saline control and sedentary (C + S); CP and sedentary (CP + S); CP and LIT (CP + LIT); CP and MIT (CP + MIT) and CP and HIIT (CP + HIIT). The training intensity was determined by a maximum running test. At the end of training, the rats received a single dose of CP (5 mg/kg), and 7 days later they were euthanized. We evaluated renal function parameters (serum creatinine, glomerular filtration rate and proteinuria), renal structure, macrophage tissue infiltration, immunolocalization of nuclear transcription factor kappa B (NF-κB), renal levels of tumor necrosis factor-alpha (TNF-α), interleukin 1ß (IL-1ß), and interleukin 6 (IL-6), and gene expression of monocyte chemoattractant protein-1 (MCP-1), toll-like receptor 4 (TLR4), and NF-κB in renal tissue. KEY FINDINGS: Although both MIT and HIIT attenuated the degree of renal injury, only the HIIT prevented changes in renal function. The three training protocols mitigated the increase in expression of all inflammatory markers, however, this effect was more pronounced in HIIT. SIGNIFICANCE: All training protocols promoted renoprotective actions, but HIIT was more effective in mitigating CP-induced acute kidney injury, in part by modulation of important markers of the innate immune response.