Dry eye disease (DED) is a common inflammatory disease of the eye surface that significantly affects quality of life. The present study investigated the effect of a propylene glycol-hydroxypropyl guar (PG-HPG) nanoemulsion on objective non-invasive ocular surface status markers in individuals with mild to moderate dry eye disease. A nonrandomized clinical trial in fifty eyes from 25 healthy subjects with mild to moderate DED who applied one drop of PG-HPG nanoemulsion to each eye twice a day for three months. The primary outcomes measured changes in tear film osmolarity and meibography scores from baseline to three months. There were statistically significant changes in meibography scores (p < 0.0001) and osmolarity (p = 0.0066) from baseline to three months. The average osmolarity decreased by approximately 6.17 units from baseline to three months. No statistically significant changes were observed in NIAVG, Schirmer’s test, or NIBUT from baseline to three months. PG-HPG Nano-emulsion produced changes in objective non-invasive ocular surface status markers, including a reduction in meibography scores and tear film osmolarity at three months, further clinical studies on the effectiveness of PG-HPG against a comparator are to expand the evidence of its effectiveness as a therapeutic option and its effects on patient quality of life in DED management.
Introduction and Objectives NASH is characterized by hepatic lipid accumulation and inflammation and Jmjd2b up-regulation has been linked with this illness progression. Pirfenidone is an antifibrotic agent with anti-inflammatory and antioxidant effects recognized to decrease NASH features. Here, we report epigenetics mechanisms related to PFD-induced histone modifications involved in experimental NASH. This study aimed to investigate PFD as an epigenetic regulator in the Jmjd2b pathway by demethylating H3k9me3 in a NASH animal model. Material and Methods Male C57BL/6J mice were fed with either normo-diet, or high fat/carbohydrate-containing diet (HF) for 16 weeks. A HF-subgroup was treated with PFD 300 mg/kg/d from week 8th to the end of protocol. Weight was recorded on weekly basis. Insulin tolerance test was performed at the end of treatment. Dual channel microarrays were hybridized to the Mus musculus genome version with 22,000 genes using hepatic mRNAs. Liver and fat histological analyses were carried out, and liver proteins were analyzed by western blot and Chromatin immunoprecipitation (ChIP). Molecular docking was used to validate binding of PFD to JMJD2BBBBB. Results Compared with HF group, mice treated with PFD reduced weight gain, hepatic fat accumulation, and epididymal fat. In addition, treatment drastically decreased cholesterol, triglycerides and VLDL, ALT and AST. Inflammatory nodules, fibrosis, and steatosis in liver tissue were also reduced. Besides, PFD modified expression of genes, such as, Jmjd2b, Pparg, Fasn and Srebp1. Likewise, PFD restored the repressive marks in H3k9, suggesting its capacity as an epigenetic regulator by decreasing Jmjd2b protein activity and interacting with its catalytic site (JmjC). Conclusions PFD played an important role as an epigenetic regulator modifying Jmjd2b activity and improving NASH features.
Microbial community control is crucial for maintaining homeostasis of the gut–liver axis in metabolic dysfunction-associated steatotic liver disease (MASLD). Here, we show that supplementation with a mixture of Mexican foodstuffs (MexMix)—Opuntia ficus indica (nopal), Theobroma cacao (cocoa) and Acheta domesticus (crickets)—enriches several beneficial taxa in MASLD mice and overweight/obese humans. Thus, MexMix induces an important prebiotic effect. In mice, a restoration of intestinal health was observed due to the increased short-chain fatty acids (SCFAs) and intestinal crypt depth, Ocln and Cldn1 expression, and decreased Il6 and Tnfa expression. MexMix significantly reduced steatosis in the mice’s liver and modified the expression of 1668 genes. By PCR, we corroborated a Tnfa and Pparg decrease, and a Cat and Sod increase. In addition, MexMix increased the hepatic NRF2 nuclear translocation and miRNA-34a, miRNA-103, and miRNA-33 decline. In overweight/obese humans, MexMix improved the body image satisfaction and reduced the fat intake. These findings indicate that this new food formulation has potential as a therapeutic approach to treat conditions associated with excessive consumption of fats and sugars.
The aim of this work was to assess the tolerability, safety, and efficacy of an ophthalmic topical formulation containing helenalin from Arnica montana and hyaluronic acid 0.4% (HA) in patients with mild-to-moderate Dry Eye Disease (DED) exhibiting positive Matrix Metalloproteinase 9 (MMP-9) test results. Tolerability and safety were evaluated in 24 healthy subjects. Participants were instructed to apply one drop of the formulation three times a day in the study eye, for 2 weeks, followed by a clinical follow-up of 21 days. Efficacy was studied in 48 DED patients randomized into Study (Group 1/receiving the studied formulation) or Control (Group 2/Receiving HA 0.4% eye lubricant) groups for 1 month. Assessments included an MMP-9 positivity test, conjunctival impression cytology (CIC), Ocular Surface Disease Index (OSDI), non-invasive film tear breakup time (NIBUT), non-invasive average breakup time (NIAvg-BUT), ocular surface staining, Schirmer’s test, and meibomiography. A crossover design with an additional 1-month follow-up was applied to both groups. Healthy subjects receiving the studied formulation exhibited good tolerability and no adverse events. Regarding the efficacy study, Group 1 exhibited a statistically significant reduction in the MMP-9 positivity rate compared to Group 2 (p < 0.001). Both Group 1 and Group 2 exhibited substantial improvements in OSDI and NIBUT scores (p < 0.001). However, Group 1 demonstrated a significant improvement in NI-Avg-BUT and Schirmer’s test scores (p < 0.001), whereas Group 2 did not (p > 0.05). Finally, after the crossover, the proportion of MMP-9-positive subjects in Group 1 increased from 25% to 91.6%, while Group 2 showed a significant decrease from 87.5% to 20.8%. Overall, the topical formulation containing sesquiterpene helenalin from Arnica montana and hyaluronic acid was well tolerated and exhibited a favorable safety profile. Our formulation reduces DED symptomatology and modulates the ocular surface inflammatory process; this is evidenced by the enhancement of CIC, the improvement of DED-related tear film status, and the reduction of the MMP-9 positivity rate.
Regenerative medicine (RM) has emerged as a promising and revolutionary solution to address a range of unmet needs in healthcare, including ophthalmology. Moreover, RM takes advantage of the body's innate ability to repair and replace pathologically affected tissues. On the other hand, despite its immense promise, RM faces challenges such as ethical concerns, host-related immune responses, and the need for additional scientific validation, among others. The primary aim of this review is to present a high-level overview of current strategies in the domain of RM (cell therapy, exosomes, scaffolds, in vivo reprogramming, organoids, and interspecies chimerism), centering around the field of ophthalmology. A search conducted on clinicaltrials.gov unveiled a total of at least 209 interventional trials related to RM within the ophthalmological field. Among these trials, there were numerous early-phase studies, including phase I, I/II, II, II/III, and III trials. Many of these studies demonstrate potential in addressing previously challenging and degenerative eye conditions, spanning from posterior segment pathologies like Age-related Macular Degeneration and Retinitis Pigmentosa to anterior structure diseases such as Dry Eye Disease and Limbal Stem Cell Deficiency. Notably, these therapeutic approaches offer tailored solutions specific to the underlying causes of each pathology, thus allowing for the hopeful possibility of bringing forth a treatment for ocular diseases that previously seemed incurable and significantly enhancing patients' quality of life. As advancements in research and technology continue to unfold, future objectives should focus on ensuring the safety and prolonged viability of transplanted cells, devising efficient delivery techniques, etc.
Introduction and Objectives: The microbial communities’ control is crucial to maintaining homeostasis of gut-liver axis; clinical evidence demonstrates disruptions of microbiota-gut-liver in individuals with Metabolic-associated fatty liver disease (MAFLD). Foods rich in fiber and polyphenols have been associated with an improvement in microbiota diversity, indexand miRNAs expression. The aim of this study was to evaluate the effect of a supplementation with a mixture of Mexican foods (MexMix): Opuntia ficus indica (nopal), Theobroma cacao (cocoa) and Acheta domesticus (crickets) on gut-liver axis in a MAFLD mice model. Materials and Patients: Thirty C57BL/6J mice were divided into three groups: 1) control: normal diet. 2) HF: high fat diet (60%) and fructose/sucrose water 3) MexMix: HF diet up to week 10, followed by HF diet supplemented with 6.7% nopal, 8.7% cocoa, and 8.7% cricket for 8 weeks. Results: The MexMix animals showed a significantly decreased in body weight, visceral and epididymal fat, adipocyte size, triglycerides, insulin, leptin, and PAI-1; while adiponectin levels increased. Using 16S rRNA gene sequencing, MexMix increased phylogenetic diversity, Firmicutes abundance, and enrichment of 10 beneficial genera, including Lachnospiraceae, Ruminococcaceae, Akkermansia, and Eubacterium_coprostanoligenes_group. In the gut, MexMix supplementation significantly increased SCFAs concentration, intestinal crypts depth, Ocln and Cldn1 expression, and decreased Il6 and Tnf-a expression. In liver, MexMix significantly reduced steatosis and Tnfa expression. Besides, MexMix increased nuclear translocation of NFR2 and, in consequence, a higher hepatic expression of Cat and Sod. MexMix also decreased hepatic expression of miRNA-34a, miRNA-103, and miRNA-33a. Conclusions: Synchronous supplementation with three nutraceuticals, nopal, cacao, and cricket, produced better results compared to previous studies where foods were administered individually. MexMix demonstrated its efficacy as a prebiotic, promoting the growth of beneficial genera and improving intestinal health. These findings indicate that MexMix has the potential to serve as a therapeutic approach for treating MAFLD in patients, as well as other conditions associated with excessive consumption of fats and sugars.
To trace the history and developments in the field of demyelinating optic neuropathies over the past two centuries.
Introduction and Objectives Metabolic-associated fatty liver disease (MAFLD) is the most common liver disease worldwide, several studies have shown that gut microbiota had a strong impact in MAFLD developing. This study aimed to evaluate the effect of a supplementation with a mixture of Mexican foods (MexMix): nopal, cacao and cricket on gut-liver axis. Materials and Methods Thirty C57BL/6J male mice were divided into three groups: 1) control group: normal diet. 2) HF group: high fat diet (60%) and water with sucrose and fructose and 3) MexMix group (MexMix): HF diet until week 10 and for 8 additional weeks; HF diet pellets supplemented with 6.7% nopal, 8.7% cocoa and 8.7% cricket. Results Mice treated with MexMix decreased body weight, visceral and epididymal fat, and adipocyte size, as well as serum levels of triglycerides, insulin, leptin, and PAI-1; while adiponectin levels increased. Using 16S rRNA gene sequencing, MexMix was shown to increase phylogenetic diversity, Firmicutes abundance, and enrichment of 10 genera, including Lachnospiraceae, Ruminococcaceae, Akkermansia, and Eubacterium_coprostanoligenes_group, associated with multiple beneficial effects such as short-chain fatty acids (SCFAs) production. In the gut, MexMix supplementation increased significantly fecal SCFAs concentration, intestinal crypts depth, Ocln and Cldn1 expression, and decreased Il6 and Tnf-a expression. In liver, MexMix significantly reduced steatosis. Liver transcriptome in MexMix group showed an enrichment in histone H3K14 acetylation pathway. Using qPCR, we confirmed higher hepatic expression of Cat, Sod and lower expression of Tnfa and Pparg. In addition, MexMix diet decreased hepatic expression of miRNA-34a, miRNA-103, and miRNA-33a. Conclusions Supplementation with MexMix demonstrated its efficacy as a prebiotic, promoting growth of beneficial genera improving intestinal health. This suggests that MexMix could be a potential therapeutic strategy for treating MAFLD in patients, as well as other conditions linked to excessive consumption of fats and sugars.
Purpose: To assess the tolerability, safety, and efficacy of an ophthalmic topical formulation containing helenalin from Arnica montana and hyaluronic acid 0.4% (HA) in patients with mild to moderate dry eye disease (DED) exhibiting positive Matrix Metalloproteinase 9 (MMP-9) test results. Methods: Tolerability and safety were evaluated in 24 healthy subjects. Participants were in-structed to routinely apply one drop of the formulation three times a day in the study eye, for a period of two weeks, followed by a clinical follow-up of 21 days. Efficacy was studied in 48 DED patients randomized into Study (Group 1/ receiving the study formulation) or Control (Group 2/ Receiving HA 0.4% eye lubricant) groups, for 4 weeks. Assessments included MMP-9 positivity, conjunctival impression cytology (CIC), Ocular Surface Disease Index (OSDI), non-invasive tear film breakup time (NIF-BUT), non-invasive average breakup time (NIAvg-BUT), ocular surface staining, Schirmer's test, and meibomiography. A crossover design with a four-week follow-up was applied to the control group. Results: Healthy subjects receiving the study formulation exhibited good tolerability and no ad-verse events. Group 1 showed significant MMP-9 reduction (25% positivity rate) unlike Group 2 (87.5% positivity rate). Group 1 displayed improved CIC (33.3% vs. 0% SSD) compared to Group 2 (29.1%). OSDI and NIF-BUT scores improved in both groups (p < 0.001). Only Group 1 showed improved NIAvg-BUT and Schirmer’s test scores (p < 0.001), while Group 2 did not (p > 0.05). MMP-9-positive subjects shifted from 25% to 91.6% in Group 1 and 87.5% to 20.8% in Group 2 after the follow-up. Conclusion: The topical formulation containing helenalin from Arnica montana and hyaluronic acid is well tolerated and has a good safety profile. Our formulation reduces DED sympto-matology and modulates the ocular surface inflammatory process; this is evidenced by the en-hancement of CIC, the improvement of DED-related tear film status, and the reduction of MMP-9 positivity rate.
Introduction and Objectives: Hepatocellular carcinoma (HCC) is the most frequent hepatic neoplasia, where oxidative, fibrogenic, proliferative, and epigenetic processes are altered. Pirfenidone (PFD) has been shown to have important hepatoprotective properties. However, its efficacy in HCC development is unknown. This study aimed to 1) To determine whether PFD has antioxidative, antifibrogenic and antiproliferative effects. 2) To determine PFD effects on epigenetic regulation mechanisms. Materials and Methods: Male Fischer-344 rats were divided into three groups. Group 1. Control, NT; Group 2. Damage, HCC, generated by diethylnitrosamine weekly administration; (50mg/kg, i.p.) and 2-acetylaminofluorene (25mg/kg, p.o.) for 12 weeks; and Group 3. HCC/PFD: with the same treatment as Group 2, plus PFD (300 mg/kg, p.o./day). Liver enzyme activity was quantified in serum; lipoperoxidation and GSH levels were evaluated in liver tissue samples; histopathological analyzes were performed. In addition, fibrogenic, antioxidant, anti-proliferative and epigenetic regulation markers were determined by Western blot. Finally, global DNA methylation was determined by Dot-blot and ELISA. The data obtained were analyzed using one-way ANOVA and a Tukey post hoc test. Results: We demonstrate that PFD treatment reduces the number and size of neoplastic lesions, prevents damage to hepatic architecture and collagen deposition, and decreases the presence of the histopathological marker Glypican-3. On the other hand, it positively regulates antioxidant markers such as GSH, MDA, Nrf2, GSTP1 and Catalase. It was also effective to decrease c-Myc expression and β-catenin redistribution from the nucleus to the cytoplasm. Finally, PFD stimulated the nuclear transfer of several isoforms of PPARs, SIRT1 and DNMT1, increasing epigenetic mechanisms of global DNA methylation (figure 1). Conclusions: PFD prevents neoplastic lesions development by modulating antifibrogenic, antioxidant, and antiproliferative processes and modulating epigenetic marks to reverse global DNA hypomethylation.
Neural tissue engineering presents a compelling technological breakthrough in restoring brain function, holding immense promise. However, the quest to develop implantable scaffolds for neural culture that fulfill all necessary criteria poses a remarkable challenge for material science. These materials must possess a host of desirable characteristics, including support for cellular survival, proliferation, and neuronal migration and the minimization of inflammatory responses. Moreover, they should facilitate electrochemical cell communication, display mechanical properties akin to the brain, emulate the intricate architecture of the extracellular matrix, and ideally allow the controlled release of substances. This comprehensive review delves into the primary requisites, limitations, and prospective avenues for scaffold design in brain tissue engineering. By offering a panoramic overview, our work aims to serve as an essential resource, guiding the creation of materials endowed with bio-mimetic properties, ultimately revolutionizing the treatment of neurological disorders by developing brain-implantable scaffolds.
Objective: Platelet-rich plasma (PRP) is used in multiple coagulation disorders. Its therapeutic effectiveness relies on technical procedures related to PRP procurement and preservation because free radicals induce platelet activation and aging. This work aims to elucidate the oxidative mechanisms involved in activation of platelets obtained from PRP during storage. Materials and Methods: One hundred ten PRP batches were obtained from healthy donors and kept under stirring at a temperature of 20-24 °C. Protein extraction was performed from platelet homogenates and plasma at different times of storage from day 1 to 20. The activities of antioxidant markers such as catalase (CAT), superoxide dismutase, and ceruloplasmin, as well as fibrinolytic protein activity metalloproteases 2 and 3, plasmin, and urokinase plasminogen activator, were analyzed by zymography assays. Oxidized proteins were also determined. Results: Significant activity of antioxidant enzymes and fibrinolytic molecules was observed on day 5 of storage in PRP homogenates, which increased over time and was concomitantly correlated with oxidized protein levels. Reverse enzymatic activity patterns were observed in plasma, except for CAT, which remained unchanged. Conclusion: Storage conditions of platelets from PRP for up to 5 days induced in vitro platelet activation by oxidative damage and proteolysis. This finding confirms the need for proper management of these blood products to preserve their viability and functionality.
Background: Ultraviolet radiation (UV) is the main environmental factor that causes histological degenerative changes of the skin giving rise to a chronic process called photodamage. Non-melanoma skin cancer induced by UVB radiation is a result of a cascade of molecular events caused by DNA damage in epidermis cells, including persistent inflammation, oxidative stress, and suppression of T cell-mediated immunity. Retinoids such as tretinoin have been widely used in skin to treat photoaging and photodamage, though its secondary adverse effects have been recognized. Pirfenidone (PFD) has emerged as an antifibrogenic, anti-inflammatory and antioxidant agent, and in this work its efficacy was evaluated in a model of UVB-induced photodamage. Methods: Epidermal, dermal, and inflammatory changes were measured by histomorphometric parameters. In addition, gene, and protein expression of key molecules in these processes were evaluated. Results: Our results revealed an anti-photodamage effect of topical PFD with absence of inflammatory skin lesions determined by dermoscopy. In addition, PFD reduced elastosis, improved organization, arrangement, and deposition of dermal collagens, downregulated several pro-inflammatory markers such as NF-kB, IL-1, IL-6 and TNFα, and decreased keratinocyte damage. Conclusion: Topical pirfenidone represents a promising agent for the treatment of cell photodamage in humans. Clinical trials need to be carried out to explore this premise.
Hepatocellular carcinoma (HCC) is the most common primary liver cancer and is the sixth most frequent cancer in the world, being the third cause of cancer-related deaths. Nonalcoholic steatohepatitis (NASH) is characterized by fatty infiltration, oxidative stress and necroinflammation of the liver, with or without fibrosis, which can progress to advanced liver fibrosis, cirrhosis and HCC. Obesity, metabolic syndrome, insulin resistance, and diabetes exacerbates the course of NASH, which elevate the risk of HCC. The growing prevalence of obesity are related with increasing incidence of NASH, which may play a growing role in HCC epidemiology worldwide. In addition, HCC initiation and progression is driven by reprogramming of metabolism, which indicates growing appreciation of metabolism in the pathogenesis of this disease. Although no specific preventive pharmacological treatments have recommended for NASH, dietary restriction and exercise are recommended. This review focuses on the molecular connections between HCC and NASH, including genetic and risk factors, highlighting the metabolic reprogramming and aberrant epigenetic alterations in the development of HCC in NASH. Current therapeutic aspects of NASH/HCC are also reviewed.
Introduction and Objectives: One of the main mechanisms in the development and progression of nonalcoholic steatohepatitis involves oxidative and endoplasmic reticulum stress. Several studies have reported therapeutic effects of Moringa oleifera leaf extracts in different animal and cellular models due to their antioxidant, anti-inflammatory and lipid-lowering effects. This study aimed to evaluate the effect of Moringa oleifera aqueous extract on biomarkers of oxidative stress in a murine model of non-alcoholic steatohepatitis. Material and methods: Characterization of the aqueous extract was performed by DPPH and ABTS spectrophotometric assays. Male C57BL/6J mice were randomized into two groups. 1) Conventional diet (ND) (n = 5) (18% lipid) and 2) High-fat diet (HF) (n = 10) (60% lipid and 42 g/L sugar in water of use) for 16 weeks. On the ninth week, five animals in the HF group were divided into a subgroup, 3) Moringa Oleifera (HF + MO), 290 mg/kg/day p.o. for eight weeks. Malondialdehyde (MDA) levels were determined in liver homogenates and the transcriptome was measured by microarrays. miRNAs involved in liver disease were also determined. Statistical analysis was performed by differences between groups determined by ANOVA or Kruskal-Wallis test. Results: Moringa aqueous extract showed antioxidant capacity; DPPH values were 10081.4 ± 0.3 and 22960.4 ± 0.3 for ABTS. Hepatic MDA levels increased in the HF group compared to the ND group (p<0.05) and decreased in the moringa-treated group (p<0.05). The transcriptome analysis demonstrated the downregulation of genes involved in endoplasmic reticulum stress. The miR-122-5p, miR-21a-5p, miR-34a-5p and miR-103-3p decreased in the MO-treated group. Conclusions: Moringa oleifera treatment might be considered a therapeutic alternative for the NASH spectrum of liver disorders.
Ophthalmic drug delivery to the posterior segment of the eye has been challenging due to the complex ocular anatomy. Intravitreal injection of drugs was introduced to deliver therapeutic doses in the posterior segment. Different posterior segment diseases including age-related macular degeneration, diabetic macular edema, retinal vein occlusions, uveitis, and cystoid macular edema, among others, have been historically treated with intravitreal corticosteroids injections, and more recently with intravitreal corticosteroids drug implants. Triamcinolone acetonide (TA) is the most frequently used intraocular synthetic corticosteroid. Using nanoparticle-based TA delivery systems has been proposed as an alternative to intravitreal injections in the treatment of posterior segment diseases. From these novel delivery systems, topical liposomes have been the most promising strategy. This review is oriented to exhibit triamcinolone acetonide drug evolution and its results in treating posterior segment diseases using diverse delivery platforms.
Introduction and Objectives: Hepatocellular carcinoma (HCC) is the most frequent hepatic neoplasia, where oxidative, fibrogenic, proliferative, and epigenetic processes are altered. Pirfenidone (PFD) has been shown to have important hepatoprotective properties. However, its efficacy in HCC development is unknown. This study aimed to 1) determine whether PFD has antioxidative, antifibrogenic and antiproliferative effects and 2) determine PFD effects on epigenetic regulation mechanisms. Materials and Methods: Male Fischer-344 rats were divided into three groups. Group 1. Control, NT; Group 2. Damage, HCC, generated by diethylnitrosamine weekly administration; (50mg/kg, i.p.) and 2-acetylaminofluorene (25mg/kg, p.o.) for 12 weeks; and Group 3. HCC/PFD: with the same treatment as Group 2, plus PFD (300 mg/kg, p.o./day). Liver enzyme activity was quantified in serum; lipoperoxidation and GSH levels were evaluated in liver tissue samples; histopathological analyzes were performed. In addition, fibrogenic, antioxidant, anti-proliferative and epigenetic regulation markers were determined by Western blot. Finally, global DNA methylation was determined by Dot-blot and ELISA. The data obtained were analyzed using one-way ANOVA, and a Tukey post hoc test. Results: We demonstrate that PFD treatment reduces the number and size of neoplastic lesions, prevents damage to hepatic architecture and collagen deposition, and decreases the presence of the histopathological marker Glypican-3. On the other hand, it positively regulates antioxidant markers such as GSH, MDA, Nrf2, GSTP1 and Catalase. It was also effective to decrease c-Myc expression and β-catenin redistribution from the nucleus to the cytoplasm. Finally, PFD stimulated the nuclear transfer of several isoforms of PPARs, SIRT1 and DNMT1, increasing epigenetic mechanisms of global DNA methylation (figure 1). Conclusions: PFD prevents neoplastic lesions development by modulating antifibrogenic, antioxidant, and antiproliferative processes and modulating epigenetic marks to reverse global DNA hypomethylation.
Diet containing Mexican ancestral foods such as cocoa, nopal, avocado, and common bean have been individually reported to have beneficial effects on obesity and comorbidities. Methods: A systematic review and meta-analysis on the effect of Mexican ancestral foods on the anthropometric, lipid, and glycemic control variables in obese patients was performed following PRISMA guidelines. Data were analyzed using a random-effects model. Results: We selected 4664 articles from an initial search, of which only fifteen studies satisfied the inclusion criteria. Data for 1670 participants were analyzed: 843 in the intervention group and 827 in the control group. A significant reduction in body mass index (mean difference: -0.80 (-1.31 to -0.30)) (95% confidence interval), p = 0.002, heterogeneity I-2 = 92% was showed after the ingestion of cocoa, nopal, avocado, or common bean. The mean difference for body weight was -0.57 (-1.93 to 0.79), waist of circumference: -0.16 (-2.54 to -2.21), total cholesterol: -5.04 (-11.5 to 1.08), triglycerides: -10.11 (-27.87 to 7.64), fasting glucose: -0.81 (-5.81 to 4.19), and insulin: -0.15 (-0.80 to 0.50). Mexican ancestral food supplementation seems to improve anthropometric, lipid, and glycemic control variables in obesity; however, more randomized controlled trials are needed to have further decisive evidence about dosage and method of supplementation and to increase the sample size.
The development of several vaccines against the SARS-CoV2 virus and their application in millions of people have shown efficacy and safety in the transfer of genes to muscle turning this tissue into a protein-producing factory. Established advanced liver fibrosis, is characterized by replacement of hepatic parenchyma by tissue scar, mostly collagen type I, with increased profibrogenic and proinflammatory molecules gene expression. Matrix metalloproteinase 8 (MMP-8) is an interstitial collagen-degrading proenzyme acting preferentially on collagen type I when activated. This study was carried out to elucidate the effect of an intramuscularly delivered adenoviral vector containing proMMP-8 gene cDNA (AdhMMP8) in male Wistar rats with experimental advanced liver fibrosis induced by thioacetamide. Therapeutic effects were monitored after 1, 2, or 3 weeks of a single dose (3 × 1011 vp/kg) of AdhMMP8. Circulating and liver concentration of MMP-8 protein remained constant; hepatic fibrosis decreased up to 48%; proinflammatory and profibrogenic genes expression diminished: TNF-α 2.28-fold, IL-1 1.95-fold, Col 1A1 4-fold, TGF-β1 3-fold and CTGF 2-fold; and antifibrogenic genes expression raised, MMP-9 2.8-fold and MMP-1 10-fold. Our data proposes that the administration of AdhMMP8 in muscle is safe and effective in achieving liver fibrosis regression at a comparable extent as when the adenoviral vector is delivered systemically to reach the liver, using a minimally invasive procedure.
Aim: Assess the in vitro effect of hepatitis B virus (HBV) genotype H (HBV/H) with the small surface HBV protein (HBs) C107R mutation on hepatitis B surface antigen (HBsAg) detection, TGFB1, CAT and IFNB1A expression, and the response to IFN-β-1a treatment. Methods: HBV/H wild-type and HBs C107R variant replicons were constructed and transfected into hepatic stellate cells and/or Huh7 that were later treated with IFN-β-1a. HBsAg, HBV-DNA, pgRNA, TGFB1, CAT and IFNB1A expression was analyzed. 3D HBs structure from wild-type and C107R were foreseen by AlphaFold protein predictor, and IFN-β-1a antiviral effect was evaluated. Results: C107R mutation did not impact viral replication, but HBsAg serologic detection was affected. Wild-type and C107R similarly modified gene expression and responded to IFN-β-1a. Conclusion: C107R disrupts the Cys107/Cys138 disulfide bond and impairs HBsAg detection. Independently of the mutation, there were changes in TGFB1, CAT and IFNB1A expression, and a medium response to IFN-β-1a treatment compared with genotype A and C.