Detection and activity of MMP-2 and MMP-9 in Leishmania amazonensis and Leishmania braziliensis promastigotes.

Metalloproteinases (MMPs) are remarkable zinc-dependent endopeptidases, critical for degrading components of the extracellular matrix, thus actively influencing cell migration. Their impact on intracellular parasites, such as the enigmatic protozoan Leishmania, elicits intriguing queries. This study explores into the untapped territory of MMP-2 and MMP-9 within Leishmania spp. promastigotes. Notably, we successfully detected and quantified these MMPs, while also evaluating their activity in two distinct Leishmania species-L. amazonensis (La) and L. braziliensis (Lb)-at various growth stages and isolated from distinct clinical tegumentar disease forms. The results unveiled the presence of MMP-2 and MMP-9 in both species, albeit with distinct localization patterns. Specifically, MMP-9 exhibited significantly higher gelatinolytic activity in La when compared to Lb. Moreover, our data cleverly illustrated the presence and release of MMP-2 and MMP-9 by La and Lb promastigotes, exposing their ability to invade and migrate within a collagen matrix. This pioneering study establishes a compelling correlation between MMP-2 and MMP-9 and their potential role in the dynamics of La and Lb infection. Suggesting their potential as prognostic markers for severe leishmaniasis and promising target molecules for therapeutic interventions, this research opens new avenues for combatting this debilitating parasitic disease.

Imbalance of Peripheral Temperature, Sympathovagal, and Cytokine Profile in Long COVID.

A persistent state of inflammation has been reported during the COVID-19 pandemic. This study aimed to assess short-term heart rate variability (HRV), peripheral body temperature, and serum cytokine levels in patients with long COVID. We evaluated 202 patients with long COVID symptoms categorized them according to the duration of their COVID symptoms (≤120 days, n = 81; >120 days, n = 121), in addition to 95 healthy individuals selected as controls. All HRV variables differed significantly between the control group and patients with long COVID in the ≤120 days group (p < 0.05), and participants in the long COVID ≤120 days group had higher temperatures than those in the long COVID >120 days group in all regions analysed (p < 0.05). Cytokine analysis showed higher levels of interleukin 17 (IL-17) and interleukin 2 (IL-2), and lower levels of interleukin 4 (IL-4) (p < 0.05). Our results suggest a reduction in parasympathetic activation during long COVID and an increase in body temperature due to possible endothelial damage caused by the maintenance of elevated levels of inflammatory mediators. Furthermore, high serum levels of IL-17 and IL-2 and low levels of IL-4 appear to constitute a long-term profile of COVID-19 cytokines, and these markers are potential targets for long COVID-treatment and prevention strategies.

Chest Computed Tomography Is an Efficient Method for Initial Diagnosis of COVID-19: An Observational Study.

Coronavirus disease (COVID-19) is an infectious disease that can lead to pneumonia, pulmonary oedema, acute respiratory distress syndrome, multiple organ and system dysfunction, and death. This study aimed to verify the efficacy of chest computed tomography (CT) for the initial diagnosis of COVID-19. This observational, retrospective, cross-sectional study included 259 individuals who underwent clinical evaluation, blood collection, chest CT, and a reverse transcription polymerase chain reaction (RT-PCR) diagnostic test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during their course of treatment at a reference hospital in Belém, Pará, Brazil between April and June 2020. Inclusion criteria were flu-like symptoms in adults of both sexes. Individuals with an inconclusive COVID-19 molecular test or who had artifacts in the chest CT images were excluded. Parametric data were analyzed using Student-t-test and non-parametric data were analyzed using average test and Fisher exact test. Participants were divided into two groups: Group 1 (COVID-19 positive), n = 211 (124 males, 87 females), 51.8 ± 17.9 years old and Group 2 (COVID-19 negative), n = 48 (22 males, 26 females), 47.6 ± 18.6 years old. Most frequent symptoms were cough [Group 1 n = 199 (94%)/Group 2 n = 46 (95%)], fever [Group 1 n = 154 (72%)/Group 2 n = 28 (58%)], myalgia [Group 1 n = 172 (81%)/Group 2 n = 38 (79%)], dyspnoea [Group 1 n = 169 (80%) / Group 2 n = 37 (77%)], headache [Group 1 n = 163 (77%)/Group 2 n = 32 (66%)], and anosmia [Group 1 n = 154 (73%)/Group 2 n = 29 (60%)]. Group 1 had a higher proportion of ground-glass opacity [Group 1 n = 175 (83%)/Group 2 n = 24 (50%), 0.00], vascular enhancement sign [Group 1 n = 128 (60%)/Group 2 n = 15 (31%), 0.00], septal thickening [Group 1 n = 99 (47%)/Group 2 n = 13 (27%), 0.01], crazy-paving pattern [Group 1 n = 98 (46%) / Group 2 n = 13 (27%), 0.01], consolidations [Group 1 n = 92 (43%)/Group 2 n = 8 (16%), 0.00], and CO-RADS 4 and 5 [Group 1 n = 163 (77.25%)/Group 2 n = 24 (50%), 0.00] categories in chest CT. Chest CT, when available, was found to be an efficient method for the initial diagnosis and better management of individuals with COVID-19.

Computed tomography with 6-year follow-up demonstrates the evolution of HTLV-1 related lung injuries: A cohort study.

Previous observational studies have demonstrated the development of pulmonary impairments in human T-lymphotropic virus type 1 (HTLV-1) infected individuals. The main observed lesions due to chronic inflammation of viral infection in situ are bronchiectasis and lung-scarring injuries. This lung inflammation may be the causal agent of restrictive and obstructive lung diseases, primarily in tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP-HAM) patients. We conducted a prospective cohort study to compare spirometry and high-resolution computed tomography (HRCT) findings among 28 HTLV-1-carrier patients over the course of 6 years (2014-2019) (male/female: 7/21; mean age: 54.7 ± 9.5, range: 41-68 years). Chest HRCT exams revealed the development and evolution of lung lesions related to TSP-HAM: including centrilobular nodules, parenchymal bands, lung cysts, bronchiectasis, ground-glass opacity, mosaic attenuation, and pleural thickening. Spirometry exams showed maintenance of respiratory function, with few alterations in parameters suggestive of obstructive and restrictive disorders primarily in individuals with lung lesions and TSP-HAM. The findings of the present study indicate that pulmonary disease related to HTLV-1 is a progressive disease, with development of new lung lesions, mainly in individuals with TSP-HAM. To improve clinical management of these individuals, we recommend that individuals diagnosed with PET-MAH undergo pulmonary evaluation.

A protocol of hepatic volume measurement using magnetic resonance imaging in individuals from the Eastern Brazilian Amazon population.

Determination of hepatic volume is an important preoperative procedure and is done through imaging exams or standard liver volume (SLV) formulas developed based on the biotype of each population. In the absence of a specific SLV formula for the Brazilian Eastern Amazon population, the measurement of liver volume is made with reference values from other populations. The aim of study was to compare the hepatic volume in healthy residents from the Brazilian Eastern Amazon population obtained with magnetic resonance imaging (MRI) and recommended SLV formulas validated to other populations. This was a Observational, cross-sectional study. Anthropometric data of 42 healthy individuals aged 18-60 years of both sexes was collected to measure the liver volume through SLV formulas calculations and MRI. MRI shows similarity with the Western European SLV liver volume values and significant differences with the Japan SLV formula, mainly for women, with a moderate-to-weak correlation with the MRI measurements. There was a strong correlation between weight and body surface area in male patients analysed with measurements of the liver volume by the MRI and SLV formulas. The SLV formula based on the Western European population could be used in the absence of a specific formula for individuals living in the Amazon region. The results suggest that liver measurement formulas should take into consideration the sex of individuals, as well as the development of a specific SLV formula for the Eastern Amazon population and the conduction of similar studies in other Brazilian regions.

Doppler ultrasonography: A non-invasive method used to diagnose and follow up patients with chronic hepatitis C.

BACKGROUND AND AIM: This study aimed to investigate the association between the findings of Doppler ultrasonography and transient elastography using FibroScan and to determine the cut-off points, sensitivity, and specificity of resistance indices, and pulsatility of the hepatic vessels to predict significant hepatic fibrosis. METHODS: This is a transversal, observational, and analytical study that includes 30 patients with chronic hepatitis C who were admitted at a public referral hospital. Transient elastography and ultrasonographic data were collected, and the linear association between these methods was evaluated using the Pearson test. Various Doppler velocimetric indices were compared according to the presence/absence of significant (≥ F2) fibrosis. RESULTS: There was a moderate-strong linear association between the FibroScan data and the Doppler velocimetric indices and splenic index in the hepatic vessels; the mean values of the indices differed between groups with absent/mild (F0/F1) and significant (≥ F2) hepatic fibrosis. There was an association between the monophasic and biphasic wave pattern of the suprahepatic veins and the stratification of hepatic fibrosis estimated by the values of kilopascal in FibroScan. CONCLUSION: Doppler ultrasonography is a non-invasive method used to evaluate liver fibrosis, and it presents acceptable sensitivity/specificity for the prediction of fibrosis ≥ F2 in patients with chronic hepatitis C.

Nerve Growth Factor and Pathogenesis of Leprosy: Review and Update.

Neurotrophins are a family of proteins that regulate different aspects of biological development and neural function and are of great importance in neuroplasticity. This group of proteins has multiple functions in neuronal cells, as well as in other cellular populations. Nerve growth factor (NGF) is a neurotrophin that is endogenously produced during development and maturation by multiple cell types, including neurons, Schwann cells, oligodendrocytes, lymphocytes, mast cells, macrophages, keratinocytes, and fibroblasts. These cells produce proNGF, which is transformed by proteolytic cleavage into the biologically active NGF in the endoplasmic reticulum. The present review describes the role of NGF in the pathogenesis of leprosy and its correlations with different clinical forms of the disease and with the phenomena of regeneration and neural injury observed during infection. We discuss the involvement of NGF in the induction of neural damage and the pathophysiology of pain associated with peripheral neuropathy in leprosy. We also discuss the roles of immune factors in the evolution of this pathological process. Finally, we highlight avenues of investigation for future research to broaden our understanding of the role of NGF in the pathogenesis of leprosy. Our analysis of the literature indicates that NGF plays an important role in the evolution and outcome of Mycobacterium leprae infection. The findings described here highlight an important area of investigation, as leprosy is one of the main causes of infection in the peripheral nervous system.

Correction: CT Chest and pulmonary functional changes in patients with HTLV-associated myelopathy in the Eastern Brazilian Amazon.

[This corrects the article DOI: 10.1371/journal.pone.0186055.].

CT Chest and pulmonary functional changes in patients with HTLV-associated myelopathy in the Eastern Brazilian Amazon.

The aim of this study was to compare computed tomography (CT) scans of chest and lung function among patients with Human T-Lymphotropic Virus Type 1 (HTLV) with and without HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). In this cross-sectional study performed between January 2013 and June 2016, we included 48 patients with HAM/TSP (19 women and 11 men) and without HAM/TSP (12 women and 6 men). We compared CT findings and lung functions of these groups. Patients who had HAM/TSP had abnormal CT findings (P = 0.000), including more frequent bronchiectasis (P = 0.049), parenchymal bands (P = 0.007), interlobular septal thickening (P = 0.035), and pleural thickening (P = 0.009). In addition, neither patients with HAM/TSP (9/30; 30%) nor the controls (0/18; 0%) had obstructive or restrictive lung disease (P = 0.009). HTLV diagnosis should be considered in all patients with abnormal CT findings in whom no other cause is apparent. It is important to remember that lung disease increases the rates of morbidity and mortality in developing countries.

Mechanisms of human cytomegalovirus infection with a focus on epidermal growth factor receptor interactions.

Human cytomegalovirus (HCMV) is a widespread opportunistic herpesvirus that causes severe diseases in immunocompromised individuals. It has a high prevalence worldwide that is linked with socioeconomic factors. Similar to other herpesviruses, HCMV has the ability to establish lifelong persistence and latent infection following primary exposure. HCMV infects a broad range of cell types. This broad tropism suggests that it may use multiple receptors for host cell entry. The identification of receptors used by HCMV is essential for understanding viral pathogenesis, because these receptors mediate the early events necessary for infection. Many cell surface components have been identified as virus receptors, such as epidermal growth factor receptor (EGFR), which is characterized by tyrosine kinase activity and plays a crucial role in the control of key cellular transduction pathways. EGFR is essential for HCMV binding, signaling, and host cell entry. This review focuses on HCMV infection via EGFR on different cell types and its implications for the cellular environment, viral persistence, and infection.

Use of refrigerant spray of a propane/butane/isobutane gas mixture in the management of keratocystic odontogenic tumors: a preliminary study.

PURPOSE: Keratocystic odontogenic tumor (KCOT) is an aggressive benign tumor and the management by complete enucleation followed by cryotherapy maintains the inorganic bone matrix, resulting in better repair and reduces the rates of recurrence. A refrigerant spray with a propane/butane/isobutane gas mixture has been pointed to as an alternative to liquid nitrogen, because the device is easy to handle and contain within the cavity, providing better control and lower risk of injury to the adjacent soft tissue. Thus, the aim of this study was to evaluate the outcome of enucleation followed by cryosurgery using a refrigerant spray of this gas mixture in ten patients diagnosed with KCOT. METHOD: The biggest lesions received a prior treatment consisting of marsupialization to decrease the tumor size. During the surgeries, the lesions were removed by enucleation and the surgical site was sprayed with the gas mixture. RESULTS: Wound dehiscence was observed in all cases, which healed by the second intention. The mean follow-up period was 64.3 months (range 24-120 months). Eight of the ten patients showed no evidence of clinical or radiographic recurrence. Pathologic fractures and infections were not observed. CONCLUSIONS: The results obtained suggest that enucleation followed by cryosurgery is an effective therapy for managing KCOT.

A novel cell line derived from pleomorphic adenoma expresses MMP2, MMP9, TIMP1, TIMP2, and shows numeric chromosomal anomalies.

Pleomorphic adenoma is the most common salivary gland neoplasm, and it can be locally invasive, despite its slow growth. This study aimed to establish a novel cell line (AP-1) derived from a human pleomorphic adenoma sample to better understand local invasiveness of this tumor. AP-1 cell line was characterized by cell growth analysis, expression of epithelial and myoepithelial markers by immunofluorescence, electron microscopy, 3D cell culture assays, cytogenetic features and transcriptomic study. Expression of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) was also analyzed by immunofluorescence and zymography. Furthermore, epithelial and myoepithelial markers, MMPs and TIMPs were studied in the tumor that originated the cell line. AP-1 cells showed neoplastic epithelial and myoepithelial markers, such as cytokeratins, vimentin, S100 protein and smooth-muscle actin. These molecules were also found in vivo, in the tumor that originated the cell line. MMPs and TIMPs were observed in vivo and in AP-1 cells. Growth curve showed that AP-1 exhibited a doubling time of 3.342 days. AP-1 cells grown inside Matrigel recapitulated tumor architecture. Different numerical and structural chromosomal anomalies were visualized in cytogenetic analysis. Transcriptomic analysis addressed expression of 7 target genes (VIM, TIMP2, MMP2, MMP9, TIMP1, ACTA2 e PLAG1). Results were compared to transcriptomic profile of non-neoplastic salivary gland cells (HSG). Only MMP9 was not expressed in both libraries, and VIM was expressed solely in AP-1 library. The major difference regarding gene expression level between AP-1 and HSG samples occurred for MMP2. This gene was 184 times more expressed in AP-1 cells. Our findings suggest that AP-1 cell line could be a useful model for further studies on pleomorphic adenoma biology.

EGFR signaling downstream of EGF regulates migration, invasion, and MMP secretion of immortalized cells derived from human ameloblastoma.

Ameloblastoma is an odontogenic tumor characterized by local invasiveness and frequent recurrence. The surrounding stroma, composed of different cell types and extracellular matrix (ECM), may influence ameloblastoma invasive behavior. Furthermore, tumor and stromal cells secrete matrix metalloproteases (MMPs), which, in turn, can modulate the matrix and promote the release of ECM-bound growth factors. Among these growth factors, epidermal growth factor (EGF) and its receptor, EGFR, have already been shown to stimulate MMP synthesis, suggesting that an interdependent mechanism, involving MMP activity and growth factors release, may contribute to tumor invasiveness. The aim of this study was to evaluate the effects of the EGF/EGFR signaling pathway on migration, invasion, and MMP activity, in a primary cell line derived from human ameloblastoma. We established and characterized a primary cell line (AME-1) from a human ameloblastoma sample. This cell line was transduced with human papillomavirus type 16 (HPV16) E6/E7 oncogenes, generating the AME-HPV continuous cell line. EGF, MMP2, and MMP9 expression in ameloblastoma biopsies and in the AME-HPV cell line was analyzed by immunohistochemistry and immunofluorescence, respectively. Migratory activity of EGF-treated AME-HPV cells was investigated using monolayer wound assays and Transwell chambers. EGF-induced invasion was assessed in Boyden chambers coated with Matrigel. Conditioned medium from EGF-treated cells was subjected to zymography. EGFR expression in AME-HPV cells was silenced by small interfering RNA (siRNA), to verify the relationship between this receptor and MMP secretion. Ameloblastoma samples and AME-HPV cells expressed EGF, EGFR, MMP2, and MMP9. AME-HPV cells treated with EGF showed increased rates of migration and invasion, as well as enhanced MMP2 and MMP9 activity. EGFR knockdown decreased MMP2 and MMP9 levels in AME-HPV cells. EGFR signaling downstream of EGF probably regulates migration, invasion, and MMP secretion of ameloblastoma-derived cells.

Enxerto dermogorduroso para tratamento da atrofia hemifacial progressiva / Dermis-fat Graft for Treatment of the Progressive Hemifacial Atrophy

A atrofia hemifacial progressiva (síndrome de Parry-Romberg) é uma doença rara, de etiologia desconhecida, caracterizada por atrofia facial unilateral, que afeta pele, subcutâneo, músculo e, raramente, estruturas osteocartilaginosas. As deformidades faciais, causadas pela doença, causam transtornos psicológicos e sociais aos pacientes acometidos. O tratamento consiste na correção dessas deformidades por meio da reposição de tecido que foi perdido em função da atrofia. Preenchimento com enxertos dérmico, gorduroso, cartilaginoso ou ósseo, injeção de silicone ou próteses de acrílico são alternativas sugeridas para correção da atrofia facial. O objetivo deste estudo é relatar um caso de atrofia hemifacial progressiva, tratada com enxerto dermogorduroso e demonstrar que essa manobra cirúrgica pode melhorar o aspecto estético da face do paciente com base na discussão dos aspectos terapêuticos dessa desordem... (AU)

The progressive hemifacial atrophy (Parry-Romberg syndrome) is a rare disease of unknown etiology characterized by unilateral facial atrophy that affects skin, subcutaneous tissue, muscle, and rarely osteocartilaginous structures. Facial deformities caused by the disease cause social and psychological problems to affected patients. Treatment consists of correction of these deformities by replacing tissue that has been lost due to atrophy. Fill with grafts of dermal, fat, cartilage or bone, injection of silicone or acrylic prostheses are alternatives suggested to correct the facial atrophy. The aim of this study is to report a case of progressive hemifacial atrophy treated with dermis-fat graft and demonstrate that this surgical procedure may improve the aesthetic appearance of the patient's face and discuss the therapeutic aspects of this disorder... (AU)

Management of locally aggressive mandibular tumours using a gas combination cryosurgery.

This study evaluated the results of curettage followed by cryosurgery using a combination of propane, butane, and isobutane gas for several benign but locally aggressive bone tumours on the mandible. Twenty-nine patients (16 men and 13 women) participated in the study. Patient ages ranged from 6 to 87 years (mean, 23.72 years). Before enucleation and cryosurgery, some patients received prior treatment consisting of marsupialisation to decrease tumour size. Twenty-seven of the 29 patients (93.10%) showed no evidence of clinical or radiographic recurrence after treatment through enucleation and cryosurgery. Wound dehiscence, which was observed in all cases, healed by second intention. The average follow-up period was 70.55 months (range, 53-120 months). These results suggest that enucleation followed by cryosurgery is an effective therapy for managing locally aggressive mandible tumours. In addition, this treatment is a less expensive intervention than more radical procedures.