The Effects of COVID-19 on Healthcare Workers and Non-Healthcare Workers in Mexico: 14 Months into the Pandemic.

Background and Objectives: Healthcare workers (HCWs) play important roles in mitigating the COVID-19 pandemic and are more likely to become infected with COVID-19. Mexico, among other countries, had a high incidence and prevalence of cases and deaths from this disease. Material and Methods: This retrospective study evaluated the clinical characteristics as well as the geographical distribution of cases, deaths, and active cases of COVID-19 in HCWs and non-HCWs using official information from the Ministry of Health of Mexico. Results: A total of 235,343 cases of COVID-19 were reported in healthcare workers, and 2,094,191 cases were reported in non-healthcare workers. A total of 76.0% of cases in healthcare workers occurred in those who were between 25 and 50 years of age, and 71.4% of deaths occurred in those who were 50 to 69 years of age. Among healthcare workers, the most frequent comorbidities were obesity (15.2%), hypertension (10.9%), and diabetes (6.8%). Nurses were the group with the most cases (39.7%), followed by other healthcare workers (30.6%), physicians (26%), and dentists (1.6%). Physicians were the group with the most deaths (46%), followed by other professionals (30%), nurses (19%), and dentists (3%). Conclusion: These findings are likely the result of healthcare workers in Mexico being at a greater risk of exposure to SARS-CoV-2.

The Transcription Factor SCX is a Potential Serum Biomarker of Fibrotic Diseases.

Fibrosing diseases are causes of morbidity and mortality around the world, and they are characterized by excessive extracellular matrix (ECM) accumulation. The bHLH transcription factor scleraxis (SCX) regulates the synthesis of ECM proteins in heart fibrosis. SCX expression was evaluated in lung fibroblasts and tissue derived from fibrotic disease patients and healthy controls. We also measured SCX in sera from 57 healthy controls, and 56 Idiopathic Pulmonary Fibrosis (IPF), 40 Hypersensitivity Pneumonitis (HP), and 100 Systemic Sclerosis (SSc) patients. We report high SCX expression in fibroblasts and tissue from IPF patients versus controls. High SCX-serum levels were observed in IPF (0.663 ± 0.559 ng/mL, p < 0.01) and SSc (0.611 ± 0.296 ng/mL, p < 0.001), versus controls (0.351 ± 0.207 ng/mL) and HP (0.323 ± 0.323 ng/mL). Serum levels of the SCX heterodimerization partner, TCF3, did not associate with fibrotic illness. IPF patients with severely affected respiratory capacities and late-stage SSc patients presenting anti-topoisomerase I antibodies and interstitial lung disease showed the highest SCX-serum levels. SCX gain-of-function induced the expression of alpha-smooth muscle actin (α-SMA/ACTA2) in fibroblasts when co-overexpressed with TCF3. As late and severe stages of the fibrotic processes correlated with high circulating SCX, we postulate it as a candidate biomarker of fibrosis and a potential therapeutic target.

High glucose induces O-GlcNAc glycosylation of the vitamin D receptor (VDR) in THP1 cells and in human macrophages derived from monocytes.

Chronic hyperglycemia increases the carbon flux through the hexosamine pathway, allowing the accumulation of UDP-GlcNAc. UDP-GlcNAc is the sugar donor for the enzyme-mediated protein glycosylation event known as OGlcNAcylation. This posttranslational modification targets several transcription factors implicated in glucose toxicity, insulin resistance, and diabetes. Vitamin D plays an important role in glucose homeostasis and insulin secretion through transcriptional mechanisms mediated by its receptor (VDR). Vitamin D deficiency has been associated with higher susceptibility to bacterial diseases in diabetic patients. However, it has not been explored whether VDR is subject to OGlcNAcylation or whether high glucose affects its transcriptional or biological activities. The aim of this study was to evaluate the effect of hyperglycemia on VDR OGlcNAcylation and its effects on vitamin D-mediated transcription. We predicted potential OGlcNAcylation sites using free software. Our results showed that hyperglycemia (30 mM) induces the OGlcNAcylation of VDR in THP1 cells and in human macrophages derived from monocytes (MDM). This condition did not hamper the vitamin D-dependent activation of LL-37 gene expression, and even did not impair the macrophage bactericidal activity. Our study provides new insight into vitamin D receptor posttranslational modification that may have relevance on the physiological responses of long-term hyperglycemia.

Low serum vitamin D levels in type 2 diabetes patients are associated with decreased mycobacterial activity.

BACKGROUND: Concurrent diabetes mellitus and tuberculosis represent a significant health problem worldwide. Patients with diabetes mellitus have a high risk of tuberculosis, which may be mediated by an abnormal innate immune response due to hyperglycaemia or low vitamin D levels. METHODS: In the present study, we evaluated inactive vitamin D serum levels and the monocyte response to infection with M. tuberculosis, including phagocytosis of M. tuberculosis, antimycobacterial activity, LL-37, human ß defensin-2 and IL-10 gene expression and nitric oxide production, between type 2 diabetes mellitus patients (n = 51) and healthy volunteers (n = 38). RESULTS: Twenty-seven type 2 diabetes mellitus patients had inadequate inactive vitamin D levels (<50 nM). The percentages of M. tuberculosis phagocytosis between monocytes were similar across groups according to microscopy. Intracellular mycobacterial growth was similar in infected monocytes from both groups. However, M. tuberculosis growth was significantly higher in monocytes obtained from type 2 diabetes mellitus patients and lower vitamin D levels after 1-h (D0) and 72-h (D3) post-infection (p ≤ 0.05). LL-37, human ß defensin-2 and IL-10 mRNA expression were similar between monocytes across groups; vitamin D serum levels and LL-37, human ß defensin-2 and IL-10 expression were not correlated. Nitric oxide production was significantly higher in healthy volunteers than in type 2 diabetes mellitus patients with low vitamin D serum levels at D3 post-infection (p ≤ 0.05). CONCLUSIONS: Our results show that monocytes from type 2 diabetes mellitus patients and low vitamin D serum levels show an impaired ability to control the intracellular growth of M. tuberculosis, which is not associated with significant decrease of LL-37 or human ß defensin-2 expression. Vitamin D could be the link between diabetes and tuberculosis susceptibility.

Human mesenchymal stem cell behavior on segmented polyurethanes prepared with biologically active chain extenders.

The development of elastomeric, bioresorbable and biocompatible segmented polyurethanes (SPUs) for use in tissue-engineering applications has attracted considerable interest because of the existing need of mechanically tunable scaffolds for regeneration of different tissues, but the incorporation of osteoinductive molecules into SPUs has been limited. In this study, SPUs were synthesized from poly (ε-caprolactone)diol, 4,4'-methylene bis(cyclohexyl isocyanate) using biologically active compounds such as ascorbic acid, L-glutamine, ß-glycerol phosphate, and dexamethasone as chain extenders. Fourier transform infrared spectroscopy (FTIR) revealed the formation of both urethanes and urea linkages while differential scanning calorimetry, dynamic mechanical analysis, X-ray diffraction and mechanical testing showed that these polyurethanes were semi-crystalline polymers exhibiting high deformations. Cytocompatibility studies showed that only SPUs containing ß-glycerol phosphate supported human mesenchymal stem cell adhesion, growth, and osteogenic differentiation, rendering them potentially suitable for bone tissue regeneration, whereas other SPUs failed to support either cell growth or osteogenic differentiation, or both. This study demonstrates that modification of SPUs with osteogenic compounds can lead to new cytocompatible polymers for regenerative medicine applications.

Nucleotide-oligomerizing domain-1 (NOD1) receptor activation induces pro-inflammatory responses and autophagy in human alveolar macrophages.

BACKGROUND: Nucleotide-binding oligomerizing domain-1 (NOD1) is a cytoplasmic receptor involved in recognizing bacterial peptidoglycan fragments that localize to the cytosol. NOD1 activation triggers inflammation, antimicrobial mechanisms and autophagy in both epithelial cells and murine macrophages. NOD1 mediates intracellular pathogen clearance in the lungs of mice; however, little is known about NOD1's role in human alveolar macrophages (AMs) or its involvement in Mycobacterium tuberculosis (Mtb) infection. METHODS: AMs, monocytes (MNs), and monocyte-derived macrophages (MDMs) from healthy subjects were assayed for NOD1 expression. Cells were stimulated with the NOD1 ligand Tri-DAP and cytokine production and autophagy were assessed. Cells were infected with Mtb and treated with Tri-DAP post-infection. CFUs counting determined growth control, and autophagy protein recruitment to pathogen localization sites was analyzed by immunoelectron microscopy. RESULTS: NOD1 was expressed in AMs, MDMs and to a lesser extent MNs. Tri-DAP stimulation induced NOD1 up-regulation and a significant production of IL1ß, IL6, IL8, and TNFα in AMs and MDMs; however, the level of NOD1-dependent response in MNs was limited. Autophagy activity determined by expression of proteins Atg9, LC3, IRGM and p62 degradation was induced in a NOD1-dependent manner in AMs and MDMs but not in MNs. Infected AMs could be activated by stimulation with Tri-DAP to control the intracellular growth of Mtb. In addition, recruitment of NOD1 and the autophagy proteins IRGM and LC3 to the Mtb localization site was observed in infected AMs after treatment with Tri-DAP. CONCLUSIONS: NOD1 is involved in AM and MDM innate responses, which include proinflammatory cytokines and autophagy, with potential implications in the killing of Mtb in humans.

Suicidal ideation among prisoners: analysis with a gender perspective in a five-year follow-up (2017-2022).

INTRODUCTION: There is a high incidence of self-harming behavior in the prison setting, with a suicide rate that is higher than that of the general population. Previous studies describe the association of sociodemographic, clinical, and criminological factors with the risk of suicide in the male prison population, but there is little research that specifically analyses suicidal behavior among women. The objective of this study is to analyze the characteristics of inmates who are admitted to a psychiatric unit for suicidal thoughts or attempted suicide. MATERIAL AND METHOD: Descriptive and comparative analysis of 97 inmates (68 men, 29 women) admitted to the Unidad de Hospitalización Psiquiátrica Penitenciaria de Cataluña (UHPP-C), for suicidal ideation, between January 1, 2017, and December 31, 2022. RESULTS: There are differences in terms of place of birth, with a more significant presence of African nationalities in non-national males, while foreign inmates tend to come from Latin American countries. Men have a lower mean age, longer admissions, and a higher readmission rate. They also suffer from more psychotic and addictive disorders. Women have a higher prevalence of personality disorders and affective symptoms. CONCLUSIONS: There are sociodemographic and clinical differences between male and female prison inmates who require admission for suicidal ideation. Including a gender perspective in studies on suicide risk in the prison population can provide a solid foundation for future studies, thus allowing a more complete understanding of suicidal ideation and intervention needs in the prison population.

Comparative study of iodine-doped and undoped pyrrole grafting with plasma on poly (glycerol sebacate) scaffolds and its human dental pulp stem cells compatibility.

This study addresses the morphological and chemical characterization of PGS scaffolds after (6, 12, 18, 24, and 30 min) residence in undoped pyrrole plasma (PGS-PPy) and the evaluation of cell viability with human dental pulp stem cells (hDPSCs). The results were compared with a previous study that used iodine-doped pyrrole (PGS-PPy/I). Analyses through SEM and AFM revealed alterations in the topography and quantity of deposited PPy particles. FTIR spectra of PGS-PPy scaffolds confirmed the presence of characteristic absorption peaks of PPy, with higher intensities observed in the nitrile and -C≡C- groups compared to PGS-PPy/I scaffolds, while raman spectra indicated a lower presence of polaron N+ groups. On the other hand, PGS scaffolds modified with PPy exhibited lower cytotoxicity compared to PGS-PPy/I scaffolds, as evidenced by the Live/Dead assay. Furthermore, the PGS-PPy scaffolds at 6 and 12 min, and particularly the PGS-PPy/I scaffold at 6 min, showed the best results in terms of cell viability by the fifth day of culture. The findings of this study suggest that undoped pyrrole plasma modification for short durations could also be a viable option to enhance the interaction with hDPSCs, especially when the treatment times range between 6 min and 12 min.

Altered expression pattern of immune response-related genes and isoforms in hypersensitivity pneumonitis lung fibroblasts.

Hypersensitivity pneumonitis (HP) is an immune-mediated inflammatory interstitial lung disease that may evolve to pulmonary fibrosis, a progressive disorder with a poor prognosis characterized by fibroblast activation and extracellular matrix accumulation. In HP lung fibroblasts, the gene expression of proteins involved in the interaction with the immune response, their isoforms, and how they influence their phenotype have yet to be elucidated. We analyzed the expression and splicing variants of 16 target genes involved in the interaction between HP fibroblasts and immune signaling and evaluated possible correlations with clinical data. The comparison of HP and control fibroblasts revealed distinct gene expression patterns. HP lung fibroblasts displayed an increased expression of IFI27 and PDFGRA and a downregulation of IL17RC and TGFBR3. IFI27 immunoreactive protein was markedly increased in HP lung tissues and normal fibroblasts treated with TGF-ß. Furthermore, IFI27 overexpression in normal fibroblasts increased α-SMA and decreased cell number over time. The isoform analysis showed similar expression patterns for most genes, except for the AGER receptor with increased soluble variants relative to full-length AGER in HP fibroblasts. These findings indicate important differences in the expression of genes related to the immune response by HP fibroblasts, highlighting their unique characteristics and providing further insight into a possible profibrotic role of IFI27 in the disease.

NOD2 enhances the innate response of alveolar macrophages to Mycobacterium tuberculosis in humans.

A role for the nucleotide-binding oligomerization domain 2 (NOD2) receptor in pulmonary innate immune responses has recently been explored. In the present study, we investigated the role that NOD2 plays in human alveolar macrophage innate responses and determined its involvement in the response to infection with virulent Mycobacterium tuberculosis. Our results showed that NOD2 was expressed in human alveolar macrophages, and significant amounts of IL-1ß, IL-6, and TNF-α were produced upon ligand recognition with muramyldipeptide (MDP). NOD2 ligation induced the transcription and protein expression of the antimicrobial peptide LL37 and the autophagy enzyme IRGM in alveolar macrophages, demonstrating a novel function for this receptor in these cells. MDP treatment of alveolar macrophages improved the intracellular growth control of virulent M. tuberculosis; this was associated with a significant release of TNF-α and IL-6 and overexpression of bactericidal LL37. In addition, the autophagy proteins IRGM, LC3 and ATG16L1 were recruited to the bacteria-containing autophagosome after treatment with MDP. In conclusion, our results suggest that NOD2 can modulate the innate immune response of alveolar macrophages and play a role in the initial control of respiratory M. tuberculosis infections.

Humoral and cellular responses to a non-adjuvanted monovalent H1N1 pandemic influenza vaccine in hospital employees.

BACKGROUND: The efficacy of the H1N1 influenza vaccine relies on the induction of both humoral and cellular responses. This study evaluated the humoral and cellular responses to a monovalent non-adjuvanted pandemic influenza A/H1N1 vaccine in occupationally exposed subjects who were previously vaccinated with a seasonal vaccine. METHODS: Sixty healthy workers from a respiratory disease hospital were recruited. Sera and peripheral blood mononuclear cells (PBMCs) were obtained prior to and 1 month after vaccination with a non-adjuvanted monovalent 2009 H1N1 vaccine (Influenza A (H1N1) 2009 Monovalent Vaccine Panenza, Sanofi Pasteur). Antibody titers against the pandemic A/H1N1 influenza virus were measured via hemagglutination inhibition (HI) and microneutralization assays. Antibodies against the seasonal HA1 were assessed by ELISA. The frequency of IFN-γ-producing cells as well as CD4+ and CD8+ T cell proliferation specific to the pandemic virus A/H1N peptides, seasonal H1N1 peptides and seasonal H3N2 peptides were assessed using ELISPOT and flow cytometry. RESULTS: At baseline, 6.7% of the subjects had seroprotective antibody titers. The seroconversion rate was 48.3%, and the seroprotection rate was 66.7%. The geometric mean titers (GMTs) were significantly increased (from 6.8 to 64.9, p < 0.05). Forty-nine percent of the subjects had basal levels of specific IFN-γ-producing T cells to the pandemic A/H1N1 peptides that were unchanged post-vaccination. CD4+ T cell proliferation in response to specific pandemic A/H1N1 virus peptides was also unchanged; in contrast, the antigen-specific proliferation of CD8+ T cells significantly increased post-vaccination. CONCLUSION: Our results indicate that a cellular immune response that is cross-reactive to pandemic influenza antigens may be present in populations exposed to the circulating seasonal influenza virus prior to pandemic or seasonal vaccination. Additionally, we found that the pandemic vaccine induced a significant increase in CD8+ T cell proliferation.

In Vitro and In Vivo Evaluation of a Polycaprolactone (PCL)/Polylactic-Co-Glycolic Acid (PLGA) (80:20) Scaffold for Improved Treatment of Chondral (Cartilage) Injuries.

Articular cartilage is a specialized tissue that provides a smooth surface for joint movement and load transmission. Unfortunately, it has limited regenerative capacity. Tissue engineering, combining different cell types, scaffolds, growth factors, and physical stimulation has become an alternative for repairing and regenerating articular cartilage. Dental Follicle Mesenchymal Stem Cells (DFMSCs) are attractive candidates for cartilage tissue engineering because of their ability to differentiate into chondrocytes, on the other hand, the polymers blend like Polycaprolactone (PCL) and Poly Lactic-co-Glycolic Acid (PLGA) have shown promise given their mechanical properties and biocompatibility. In this work, the physicochemical properties of polymer blends were evaluated by Fourier Transform Infrared Spectroscopy (FTIR) and Scanning Electron Microscope (SEM) and were positive for both techniques. The DFMSCs demonstrated stemness by flow cytometry. The scaffold showed to be a non-toxic effect when we evaluated it with Alamar blue, and the samples were analyzed using SEM and phalloidin staining to evaluate cell adhesion to the scaffold. The synthesis of glycosaminoglycans was positive on the construct in vitro. Finally, the PCL/PLGA scaffold showed a better repair capacity than two commercial compounds, when tested in a chondral defect rat model. These results suggest that the PCL/PLGA (80:20) scaffold may be suitable for applications in the tissue engineering of articular hyaline cartilage.

The Protective Role of Cranberries and Blueberries in Oral Cancer.

BACKGROUND: Oral cancer has a high prevalence worldwide, and this disease is caused by genetic, immunological, and environmental factors. The main risk factors associated with oral cancer are smoking and alcohol. RESULTS: There are various strategies to reduce risk factors, including prevention programs as well as the consumption of an adequate diet that includes phytochemical compounds derived from cranberries (Vaccinium macrocarpon A.) and blueberries (Vaccinium corymbosum L.); these compounds exhibit antitumor properties. RESULTS: The main outcome of this review is as follows: the properties of phytochemicals derived from cranberries were evaluated for protection against risk factors associated with oral cancer. CONCLUSIONS: The secondary metabolites of cranberries promote biological effects that provide protection against smoking and alcoholism. An alternative for the prevention of oral cancer can be the consumption of these cranberries and blueberries.

Preliminary data from a 4-year mirror-image and multicentre study of patients initiating paliperidone palmitate 6-monthly long-acting injectable antipsychotic: the Paliperidone 2 per Year study.

Background: Paliperidone palmitate 6-monthly (PP6M) is the first long-acting antipsychotic injectable (LAI) to allow for only two medication administrations per year, though there is presently limited insight into its effectiveness and potential added value in real clinical practice conditions. Objectives: To present our ongoing study and draw its preliminary data on patient characteristics initiating PP6M and adherence during the first year of treatment. Methods: The paliperidone 2 per year (P2Y) study is a 4-year, multicentre, prospective mirror-image pragmatic study taking place at over 20 different sites in Europe. The mirror period covers 2 years either side of the PP6M LAI initiation. Retrospective data for the previous 2 years are collected for each patient from the electronic health records. Prospective data are recorded at baseline, 6, 12, 18 and 24 months of drug administration and also cover information on concomitant psychiatric medication, relapses, hospital admissions, side effects, discontinuation and its reasons. Meanwhile, here we present preliminary data from the P2Y study at basal and 6-month period (first and second PP6M administration). Results: At the point of PP6M initiation, the most frequent diagnosis was schizophrenia (69%), the clinical global impression scale mean score was 3.5 (moderately markedly ill) and the rate of previous hospital admissions per patient and year was 0.21. PP6M was initiated after a median of 3-4 years on previous treatment: 146 (73%) from paliperidone palmitate 3-monthly, 37 (19%) from paliperidone palmitate 1-monthly and 17 (9%) from other antipsychotics. The mean dose of the first PP6M was 1098.9 mg. The retention rate at 6 months and 1 year of treatment on PP6M in our cohort was 94%. Conclusion: Patient and clinician preference for LAIs with longer dosing intervals was the main reason for PP6M initiation/switching resulting in high treatment persistence. Future data are needed to evaluate the full impact of PP6M in clinical practice.

Spatiotemporal Dynamic Regulation of Organelles During Meiotic Development, Insights From Fungi.

Eukaryotic cell development involves precise regulation of organelle activity and dynamics, which adapt the cell architecture and metabolism to the changing developmental requirements. Research in various fungal model organisms has disclosed that meiotic development involves precise spatiotemporal regulation of the formation and dynamics of distinct intracellular membrane compartments, including peroxisomes, mitochondria and distinct domains of the endoplasmic reticulum, comprising its peripheral domains and the nuclear envelope. This developmental regulation implicates changes in the constitution and dynamics of these organelles, which modulate their structure, abundance and distribution. Furthermore, selective degradation systems allow timely organelle removal at defined meiotic stages, and regulated interactions between membrane compartments support meiotic-regulated organelle dynamics. This dynamic organelle remodeling is implicated in conducting organelle segregation during meiotic differentiation, and defines quality control regulatory systems safeguarding the inheritance of functional membrane compartments, promoting meiotic cell rejuvenation. Moreover, organelle remodeling is important for proper activity of the cytoskeletal system conducting meiotic nucleus segregation, as well as for meiotic differentiation. The orchestrated regulation of organelle dynamics has a determinant contribution in the formation of the renewed genetically-diverse offspring of meiosis.

Effect of different exposure times on physicochemical, mechanical and biological properties of PGS scaffolds treated with plasma of iodine-doped polypyrrole.

Polyglycerol sebacate (PGS) scaffolds obtained using a leaching technique were modified with iodine-doped polypyrrole (PPy-I) in a plasma reactor in order to study the effect of exposure time on the cell viability of hDPSCs. SEM analysis showed the formation and growth of PPy-I particles as the exposure time was increased, while FTIR and XPS analysis revealed the presence of -NH- and N+ groups in the chemical composition of the surfaces, relating to the increase in the amount of PPY-I particles. The water contact angle measurements showed an increase in the scaffold's hydrophilicity with greater exposure times which was also attributed to the rising of PPy-I particles. It was also observed that PPy-I promotes the rigidity of the treated PGS scaffolds. when in direct contact with treated PGS scaffolds, cell viability improved with respect to non-treated scaffolds, however only at shorter time exposures. Extracts of plasma-treated PGS scaffolds showed high cytotoxicity as the time exposure to plasma treatment was increased.

High performance of rapid influenza diagnostic test and variable effectiveness of influenza vaccines in Mexico.

OBJECTIVES: To evaluate the performance of rapid influenza diagnostic tests (RIDT) and influenza vaccines' effectiveness (VE) during an outbreak setting. METHODS: We compared the performance of a RIDT with RT-PCR for influenza virus detection in influenza-like illness (ILI) patients enrolled during the 2016/17 season in Mexico City. Using the test-negative design, we estimated influenza VE in all participants and stratified by age, virus subtype, and vaccine type (trivalent vs quadrivalent inactivated vaccines). The protective value of some clinical variables was evaluated by regression analyses. RESULTS: We enrolled 592 patients. RT-PCR detected 93 cases of influenza A(H1N1)pdm09, 55 of AH3N2, 141 of B, and 13 A/B virus infections. RIDT showed 90.7% sensitivity and 95.7% specificity for influenza A virus detection, and 91.5% sensitivity and 95.3% specificity for influenza B virus detection. Overall VE was 33.2% (95% CI: 3.0-54.0; p = 0.02) against any laboratory-confirmed influenza infection. VE estimates against influenza B were higher for the quadrivalent vaccine. Immunization and occupational exposure were protective factors against influenza. CONCLUSIONS: The RIDT was useful to detect influenza cases during an outbreak setting. Effectiveness of 2016/17 influenza vaccines administered in Mexico was low but significant. Our data should be considered for future local epidemiological policies.

Assessment of the vascular effects of PC6 (Neiguan) using the second derivative of the finger photoplethysmogram in healthy and hypertensive subjects.

Indices obtained from the second derivative of the digital volume pulse waveform have been proposed to characterize vascular aging, arterial rigidity, and the effects of vasoactive drugs. The purpose of this study was to assess the effects of manual needling of PC6 on SD(DVP) indices in healthy and untreated hypertensive subjects. AI, B:A, and D:A indices, based on the height of the wave components of SD(DVP), in 40 healthy subjects and 25 untreated hypertensive subjects were compared. DVP was obtained by measuring infrared light transmission through the finger. For each subject, 20-min-long DVP registration was obtained. PC6 was stimulated unilaterally by manual needling for 5 min (1-6 min). In each subject, pre-acupuncture DVP indices were compared to those of during acupuncture (1 vs. 4 min) and post-acupuncture (1 vs. 18 min). In healthy subjects, AI was significantly improved when comparing the pre- to the post-acupuncture values. In hypertensive subjects, the SD(DVP) indices improved significantly as follows: the AI index when the value of pre-acupuncture comparing to that of during acupuncture and post-acupuncture values; B:A and D:A indices when the pre-comparing to post-acupuncture values. There were significant differences between healthy and hypertensive subjects in AI, B:A, and D:A at baseline and in B:A in the during acupuncture period; there were no significant differences at post-acupuncture. These results indicate that manual needling of PC6 produced acute effects on vascular pathophysiology. Moreover, PC6 needling produced changes in SD(DVP) indices related to both large artery stiffness and the reflected wave originating in small arteries.

Nordihydroguaiaretic acid (NDGA) and α-mangostin inhibit the growth of Mycobacterium tuberculosis by inducing autophagy.

Tuberculosis (TB) remains as a global health problem. The prevalence of this infection is related to the association with other diseases, such as HIV, neglect treatment and misuse of antibiotics. Hence, the identification of new drugs is required to eradicate TB. Possible alternatives to existing antibiotics include pure compounds extracted from medicinal plants, which are an important source of antimicrobial agents. The aim of this study was to evaluate the effect of nordihydroguaiaretic acid (NDGA) and α-mangostin on Mycobacterium tuberculosis growth and bacterial survival in infected macrophages derived from the human THP-1 cell line and monocytes. Our results show that both compounds directly inhibit M. tuberculosis growth in liquid medium with Minimal Inhibitory Concentrations (MIC) of 250 and 62 µg/mL respectively, likely through preventing bacterial replication. In addition, NDGA and α-mangostin were able to induce autophagy in human cells at lower concentrations (7 and 6 µg/mL, respectively) and contributed to the elimination of intracellular bacteria. NDGA and α-mangostin could be candidates for coadjuvant therapy in cases of drug-resistant TB, and their ability to enhance the immune response by promoting autophagy might contribute to TB treatment.