Herbal-based therapeutics for diabetic patients with SARS-Cov-2 infection.

Human SARS Coronavirus-2 (SARS-CoV-2) has infected more than 170 million people worldwide, being responsible for about 3.5 million deaths so far. Despite ongoing investigations, there is still more to understand the mechanism of COVID-19 infection completely. However, it has been evidenced that SARS-CoV-2 can cause Coronavirus disease (COVID-19) notably in diabetic people. Approximately 35% of the patients who died of this disease had diabetes. A growing number of studies have evidenced that hyperglycemia is a significant risk factor for severe SARS-CoV-2 infection and plays a key role in COVID-19 mortality and diabetes comorbidity. The uncontrolled hyperglycemia can produce low-grade inflammation and impaired immunity-mediated cytokine storm that fail multiple organs and sudden death in diabetic patients with SARS-CoV-2 infection. More importantly, SARS-CoV-2 infection and interaction with ACE2 receptors also contribute to pancreatic and metabolic impairment. Thus, using of diabetes medications has been suggested to be beneficial in the better management of diabetic COVID-19 patients. Herbal treatments, as safe and affordable therapeutic agents, have recently attracted a lot of attention in this field. Accordingly, in this review, we intend to have a deep look into the molecular mechanisms of diabetic complications in SARS-CoV-2 infection and explore the therapeutic potentials of herbal medications and natural products in the management of diabetic COVID-19 patients based on recent studies and the existing clinical evidence.

Case Report of 11 Years of Severe Malabsorption, Muscular Atrophy, Seizures, and Immunodeficiency Resolved After Proximal Intercessory Prayer.

We present the case of 11 years of severe malabsorption, muscular atrophy, seizures, and immunodeficiency resolved after proximal intercessory prayer (PIP). A male infant suffered from severe abdominal pain and impaired development with the introduction of solid food at age five months. The patient had previously appeared healthy, having been born to term and breastfed. Neocate and total parenteral nutrition (TPN) were prescribed, and the former was removed due to abdominal pain and diarrhea. Ultimately, the patient became completely dependent on TPN. It was concluded that he suffered from chronic, idiopathic, severe malabsorption. Development of neutropenia, hypogamma-globulinemia, and hypotonia was recorded. Medical records document atrophy and progressive deterioration of muscular symptoms. At five years of age, frontal lobe epilepsy was detected. Over the course of the disease, several genetic tests were performed. Doctors tried unsuccessfully to diagnose an underlying condition, with various mitochondriopathies and Shwachman-Diamond syndrome suggested as possible causes, but no prognosis of recovery was given. Eleven years following the initial presentation of symptoms, proximal intercessory prayer (PIP) was administered in a single session. The patient reported no unusual sensations during prayer. However, oral feedings were immediately tolerated without discomfort from that time onward. Post-PIP medical records indicate discontinuation of TPN, seizures, and seizure medications. Progressive improvement in the hematological disorders, BMI, and muscular symptoms was also observed. The present case report describes a novel association between PIP and the lasting resolution of multiple symptoms likely related to a genetic disorder. The results inform ongoing discussions about faith-based practices in health care and suggest the need for additional studies of PIP on health outcomes.

Development and validation of LC-MS/MS methods for the simultaneous quantification of sofosbuvir and its major metabolite (GS-331007) in blood plasma and cerebrospinal and seminal fluid: Application to a pilot clinical trial with a focus on Zika.

Zika still poses a threat to global health owing to its association with serious neurological conditions and the absence of a vaccine and treatment. Sofosbuvir, an anti-hepatitis C drug, has shown anti-Zika effects in animal and cell models. Thus, this study aimed to develop and validate novel LC-MS/MS methods for the quantification of sofosbuvir and its major metabolite (GS-331007) in human plasma and cerebrospinal (CSF) and seminal fluid (SF), and apply the methods to a pilot clinical trial. The samples were prepared by liquid-liquid extraction and separated using isocratic mode on Gemini C18 columns. Analytical detection was performed using a triple quadrupole mass spectrometer equipped with an electrospray ionization source. The validated ranges for sofosbuvir were 0.5-2,000 ng/mL (plasma) and 0.5-100 ng/mL (CSF and SF), while for the metabolite they were 2.0-2,000 ng/mL (plasma), 5.0-200 ng/mL (CSF) and 10-1,500 ng/mL (SF). The intra-day and inter-day accuracies (90.8-113.8%) and precisions (1.4-14.8%) were within the acceptance range. The developed methods fulfilled all validation parameters concerning selectivity, matrix effect, carryover, linearity, dilution integrity, precision, accuracy and stability, confirming the suitability of the method for the analysis of clinical samples.

Monkeypox (Mpox) virus isolation and ultrastructural characterisation from a Brazilian human sample case.

BACKGROUND: According to the last 2023 Monkeypox (Mpox) Outbreak Global Map from the Centres for Disease Control and Prevention (CDC), more than 100 countries with no Mpox infection report cases. Brazil stands out in this group and is the second country with the highest number of cases in the last outbreak. OBJECTIVE: To contribute to knowledge of the virus infection effects in a cellular model, which is important for diagnosis infections not yet included in a provider´s differential diagnosis and for developing viral inhibition strategies. METHODS: We describe a virus isolation protocol for a human clinical sample from a patient from Brazil, the viral growth in a cell model through plaque forming units (PFU) assay, reverse transcriptase polymerase chain reaction (RT-PCR) and transmission electron microscopy (TEM). FINDINGS: We follow the viral isolation in Vero cell culture from a Mpox positive clinically diagnosed sample and show the infection effects on cellular structures using a TEM. MAIN CONCLUSIONS: Understanding the impact of viral growth on cellular structures and its replication kinetics may offer better strategies for the development of new drugs with antiviral properties.

Long-term hepatic damage in high-fructose-fed C57BL/6 mice: hepatic fibrogenesis, endoplasmic reticulum stress markers, and fibrosis.

The rising fructose intake in sugar-sweetened beverages and ultra-processed foods relates to the high incidence of nonalcoholic fatty liver disease. This study aimed to examine the effects of long-term high-fructose diet intake (for 16 or 20 weeks) on progressive hepatic damage, focusing on the endoplasmic reticulum stress markers and fibrogenesis as possible triggers of liver fibrosis. Forty 3-month-old male C57BL/6J mice were randomly divided into four nutritional groups: C16 (control diet for 16 weeks), C20 (control diet for 20 weeks), HFRU16 (high-fructose diet for 16 weeks), and HFRU20 (high-fructose diet for 20 weeks). Both HFRU groups showed oral glucose intolerance and insulin resistance, but only the HFRU20 group exhibited increased inflammation. The increased lipogenic and endoplasmic reticulum stress markers triggered hepatic fibrogenesis. Hence, time-dependent perivascular fibrosis with positive immunostaining for alpha-smooth muscle actin and reelin in HFRU mice was observed, ensuring fibrosis development in this mouse model. Our study showed time-dependent and progressive damage on hepatic cytoarchitecture, with maximization of hepatic steatosis without overweight in HFRU20 mice. ER stress and liver inflammation could mediate hepatic stellate cell activation and fibrogenesis, emerging as targets to prevent NAFLD progression and fibrosis onset in this dietary model.

Effect of photobiomodulation associated with strengthening pelvic floor muscles in volunteers with urinary incontinence: a randomized, double-blinded, and placebo-controlled clinical trial.

The dysfunctions of the female pelvic floor have a great influence on the quality of life of women, in all areas, social, psychological, and sexual. Stress urinary incontinence is the clinical condition in which the woman involuntarily loses urine to efforts, such as coughing and sneezing, causing great embarrassment and affecting her quality of life. The physiotherapeutic treatments include muscle strengthening; however, muscle fatigue is present when performing the exercises. Here we investigate the effects of photobiomodulation to prevent muscle fatigue in the pelvic floor in the treatment of stress urinary incontinence, associated with a muscle strengthening exercise protocol. We used an infrared laser (808 nm, 100 mW) and 3 J/point and fluence of 107.1 J/cm2. The application was performed at 3 points on the vaginal introits and at another 3 points inside the vaginal canal cavity for the treatment of stress urinary incontinence associated with strengthening exercises with vaginal cones. Twenty-two volunteers participated in the study, divided into two groups: group 1 (laser therapy + strengthening) and group 2 (placebo laser + strengthening). In the group 1 quality of life score, the assessment (11.63 ± 4.33) was the highest score at 17 and in the reevaluation (7.81 ± 5.14) the lowest was 0 (p < 0.05). The muscular strength increased considerably (p < 0.05) for group 1, where the vast majority of patients gained more than twice the strength in the pelvic apparatus (8.36 ± 6.65 before X 13.81 ± 8.92 after). The volunteers acquired an increase in the contraction of the muscles of the pelvic apparatus (p < 0.05) (3.45 ± 1.07); after laser application, this number increased considerably (4.27 ± 0.61). Endurance had an increase of almost 50% compared to placebo, demonstrating the resistance gain in the perineal muscles (3.90 ± 2.35 X 5 ± 1.90). We concluded that photobiomodulation treatment showed significant efficacy in relation to muscle fatigue in the pelvic apparatus right after a strengthening program in women with stress urinary incontinence.

The XadA Trimeric Autotransporter Adhesins in Xylella fastidiosa Differentially Contribute to Cell Aggregation, Biofilm Formation, Insect Transmission and Virulence to Plants.

Surface adhesion strategies are widely employed by bacterial pathogens during establishment and systemic spread in their host. A variety of cell-surface appendages such as pili, fimbriae, and afimbrial adhesins are involved in these processes. The phytopathogen Xylella fastidiosa employs several of these structures for efficient colonization of its insect and plant hosts. Among the adhesins encoded in the X. fastidiosa genome, three afimbrial adhesins, XadA1, Hsf/XadA2, and XadA3, are predicted to be trimeric autotransporters with a C-terminal YadA-anchor membrane domain. We analyzed the individual contributions of XadA1, XadA2, and XadA3 to various cellular behaviors both in vitro and in vivo. Using isogenic X. fastidiosa mutants, we found that cell-cell aggregation and biofilm formation were severely impaired in the absence of XadA3. No significant reduction of cell-surface attachment was found with any mutant under flow conditions. Acquisition by insect vectors and transmission to grapevines were reduced in the XadA3 deletion mutant. While the XadA3 mutant was hypervirulent in grapevines, XadA1 or XadA2 deletion mutants conferred lower disease severity than the wild-type strain. This insight of the importance of these adhesive proteins and their individual contributions to different aspects of X. fastidiosa biology should guide new approaches to reduce pathogen transmission and disease development. [Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

EGFR Mutations and PD-L1 Expression in Early-Stage Non-Small Cell Lung Cancer: A Real-World Data From a Single Center in Brazil.

BACKGROUND: Targeted and immunotherapies are currently moving toward early-stage settings for patients with non-small cell lung cancer (NSCLC). Predictive biomarkers data are scarce in this scenario. We aimed to describe the frequency of EGFR mutations and PD-L1 expression levels in early-stage non-squamous patients with NSCLC from a large, single Brazilian oncology center. METHODS: We retrospectively evaluated patients with NSCLC diagnosed at an early-stage (IB to IIIA-AJCC seventh edition) at Barretos Cancer Hospital (n = 302). EGFR mutational status was assessed in FFPE tumor tissues using distinct methodologies (NGS, Cobas, or Sanger sequencing). PD-L1 expression was evaluated by immunohistochemistry (clone 22C3) and reported as Tumor Proportion Score (TPS), categorized as <1%, 1-49%, and ≥50%. We evaluated the association between EGFR mutational status and PD-L1 expression with sociodemographic and clinicopathological parameters by Fisher's test, qui-square test, and logistic regression. Survival analysis was assessed by the Kaplan-Meier method and Cox regression model. RESULTS: EGFR mutations were detected in 17.3% (n = 48) of cases and were associated with female sex, never smokers, and longer overall and event-free survival. PD-L1 positivity was observed in 36.7% (n = 69) of cases [TPS 1-49% n = 44(23.4%); TPS ≥50% n = 25(13.3%)]. PD-L1 positivity was associated with smoking, weight loss, and higher disease stages (IIB/IIIA). CONCLUSION: The frequencies of EGFR mutations and PD-L1 positivity were described for early-stage non-squamous patients with NSCLC. These results will be essential for guiding treatment strategies with the recent approvals of osimertinib and immunotherapy in the adjuvant setting.

Genomic Characterization of Bacillus safensis Isolated from Mine Tailings in Peru and Evaluation of Its Cyanide-Degrading Enzyme CynD.

Understanding the biochemistry and metabolic pathways of cyanide degradation is necessary to improve the efficacy of cyanide bioremediation processes and industrial requirements. We have isolated and sequenced the genome of a cyanide-degrading Bacillus strain from water in contact with mine tailings from Lima, Peru. This strain was classified as Bacillus safensis based on 16S rRNA gene sequencing and core genome analyses and named B. safensis PER-URP-08. We searched for possible cyanide-degradation enzymes in the genome of this strain and identified a putative cyanide dihydratase (CynD) gene similar to a previously characterized CynD from Bacillus pumilus C1. Sequence analysis of CynD from B. safensis and B. pumilus allow us to identify C-terminal residues that differentiate both CynDs. We then cloned, expressed in Escherichia coli, and purified recombinant CynD from B. safensis PER-URP-08 (CynDPER-URP-08) and showed that in contrast to CynD from B. pumilus C1, this recombinant CynD remains active at up to pH 9. We also showed that oligomerization of CynDPER-URP-08 decreases as a function of increased pH. Finally, we demonstrated that transcripts of CynDPER-URP-08 in B. safensis PER-URP-08 are strongly induced in the presence of cyanide. Our results suggest that the use of B. safensis PER-URP-08 and CynDPER-URP-08 as potential tool for cyanide bioremediation warrants further investigation. IMPORTANCE Despite being of environmental concern around the world due to its toxicity, cyanide continues to be used in many important industrial processes. Thus, searching for cyanide bioremediation methods is a matter of societal concern and must be present on the political agenda of all governments. Here, we report the isolation, genome sequencing and characterization of cyanide degradation capacity of a bacterial strain isolated from an industrial mining site in Peru. We characterize a cyanide dehydratase (CynD) homolog from one of these bacteria, Bacillus safensis PER-URP-08.

Neuroprotective effects of rutin on ASH neurons in Caenorhabditis elegans model of Huntington's disease.

Huntington's disease (HD) is an autosomal dominant, progressive neurodegenerative disease. It occurs due to a mutated huntingtin gene that contains an abnormal expansion of cytosine-adenine-guanine repeats, leading to a variable-length N-terminal polyglutamine (polyQ) chain. The mutation confers toxic functions to mutant huntingtin protein, causing neurodegeneration. Rutin is a flavonoid found in various plants, such as buckwheat, some teas, and apples. Our previous studies have indicated that rutin has protective effects in HD models, but more studies are needed to unravel its effects on protein homeostasis, and to discern the underlying mechanisms. In the present study, we investigated the effects of rutin in a Caenorhabditis elegans model of HD, focusing on ASH neurons and antioxidant defense. We tested behavioral changes (touch response, movement, and octanol response), measured neuronal polyQ aggregates, and assessed degeneration using a dye-filling assay. In addition, we analyzed expression levels of heat-shock protein-16.2 and superoxide dismutase-3. Overall, our data demonstrate that chronic rutin treatment maintains the function of ASH neurons, and decreases the degeneration of their sensory terminations. We propose that rutin does so in a mechanism that involves antioxidant activity by controlling the expression of antioxidant enzymes and other chaperones regulating proteostasis. Our findings provide new evidence of rutin's potential neuroprotective role in the C. elegans model and should inform treatment strategies for neurodegenerative diseases and other diseases caused by age-related protein aggregation.

In vitro α-glucosidase inhibition by Brazilian medicinal plant extracts characterised by ultra-high performance liquid chromatography coupled to mass spectrometry.

Aiming at finding natural sources of antidiabetics agents, 15 extracts from Brazilian medicinal plants of the Atlantic Forest and Amazon region were tested against α-glucosidase enzyme. Plants were selected based on the taxonomic relationships with genera including several species with antidiabetic activity. In this screening, the extracts obtained from the flowers of Hyptis monticola and the leaves of Lantana trifolia and Lippia origanoides resulted endowed with promising anti-α-glucosidase activity. The extracts from H. monticola and from L. origanoides collected in two different areas, were characterised by ultra-high performance liquid chromatography coupled to mass spectrometry. Bioassay-guided fractionation led to the identification of several enzyme inhibiting compounds, among them the mechanism of action of naringenin and pinocembrin was investigated. The two L. origanoides extracts showed differences in bioactivity and in the phytochemical profiles. The fractionation of the extract from H. monticola led to a partial loss of the inhibitory effect.

A ligand motif enables differential vascular targeting of endothelial junctions between brain and retina.

Endothelial heterogeneity has important implications in health and disease. Molecular markers selectively expressed in the vasculature of different organs and tissues are currently being explored in targeted therapies with promising results in preclinical and clinical studies. Noteworthy is the role that combinatorial approaches such as phage display have had in identifying such markers by using phage as nanoparticles and surrogates for billions of different peptides, screening noninvasively the vascular lumen for binding sites. Here, we show that a new peptide motif that emerged from such combinatorial screening of the vasculature binds selectively to blood vessels in the brain in vivo but not to vessels in other organs. Peptides containing a conserved motif in which amino acids Phenylalanine-Arginine-Tryptophan (FRW) predominate could be visualized by transmission electron microscopy bound to the junctions between endothelial cells in all areas of the brain, including the optic nerve, but not in other barrier-containing tissues, such as intestines and testis. Remarkably, peptides containing the motif do not bind to vessels in the retina, implying an important molecular difference between these two vascular barriers. Furthermore, the peptide allows for in vivo imaging, demonstrating that new tools for studying and imaging the brain are likely to emerge from this motif.

A comparative genomic analysis of Xanthomonas arboricola pv. juglandis strains reveal hallmarks of mobile genetic elements in the adaptation and accelerated evolution of virulence.

Xanthomonas arboricola pv. juglandis (Xaj) is the most significant aboveground walnut bacterial pathogen. Disease management uses copper-based pesticides which induce pathogen resistance. We examined the genetic repertoire associated with adaptation and virulence evolution in Xaj. Comparative genomics of 32 Xaj strains reveal the possible acquisition and propagation of virulence factors via insertion sequences (IS). Fine-scale annotation revealed a Tn3 transposon (TnXaj417) encoding copper resistance genes acquired by horizontal gene transfer and associated with adaptation and tolerance to metal-based pesticides commonly used to manage pathogens in orchard ecosystems. Phylogenomic analysis reveals IS involvement in acquisition and diversification of type III effector proteins ranging from two to eight in non-pathogenic strains, 16 to 20 in pathogenic strains, besides six other putative effectors with a reduced identity degree found mostly among pathogenic strains. Yersiniabactin, xopK, xopAI, and antibiotic resistance genes are also located near ISs or inside genomic islands and structures resembling composite transposons.

Galectin-3 plays a protective role in Leishmania (Leishmania) amazonensis infection.

Leishmania (L.) amazonensis is one of the species responsible for the development of cutaneous leishmaniasis in South America. After entering the vertebrate host, L. (L.) amazonensis invades mainly neutrophils, macrophages and dendritic cells. Studies have shown that gal-3 acts as a pattern recognition receptor. However, the role of this protein in the context of L. (L.) amazonensis infection remains unclear. Here, we investigated the impact of gal-3 expression on experimental infection by L. (L.) amazonensis. Our data showed that gal-3 plays a role in controlling parasite invasion, replication and the formation of endocytic vesicles. Moreover, mice with gal-3 deficiency showed an exacerbated inflammatory response. Taken together, our data shed light to a critical role of gal-3 in the host response to infection by L. (L.) amazonensis.

Genome-resolved metagenome and metatranscriptome analyses of thermophilic composting reveal key bacterial players and their metabolic interactions.

BACKGROUND: Composting is an important technique for environment-friendly degradation of organic material, and is a microbe-driven process. Previous metagenomic studies of composting have presented a general description of the taxonomic and functional diversity of its microbial populations, but they have lacked more specific information on the key organisms that are active during the process. RESULTS: Here we present and analyze 60 mostly high-quality metagenome-assembled genomes (MAGs) recovered from time-series samples of two thermophilic composting cells, of which 47 are potentially new bacterial species; 24 of those did not have any hits in two public MAG datasets at the 95% average nucleotide identity level. Analyses of gene content and expressed functions based on metatranscriptome data for one of the cells grouped the MAGs in three clusters along the 99-day composting process. By applying metabolic modeling methods, we were able to predict metabolic dependencies between MAGs. These models indicate the importance of coadjuvant bacteria that do not carry out lignocellulose degradation but may contribute to the management of reactive oxygen species and with enzymes that increase bioenergetic efficiency in composting, such as hydrogenases and N2O reductase. Strong metabolic dependencies predicted between MAGs revealed key interactions relying on exchange of H+, NH3, O2 and CO2, as well as glucose, glutamate, succinate, fumarate and others, highlighting the importance of functional stratification and syntrophic interactions during biomass conversion. Our model includes 22 out of 49 MAGs recovered from one composting cell data. Based on this model we highlight that Rhodothermus marinus, Thermobispora bispora and a novel Gammaproteobacterium are dominant players in chemolithotrophic metabolism and cross-feeding interactions. CONCLUSIONS: The results obtained expand our knowledge of the taxonomic and functional diversity of composting bacteria and provide a model of their dynamic metabolic interactions.

Genetic Evidence and Host Immune Response in Persons Reinfected with SARS-CoV-2, Brazil.

The dynamics underlying severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection remain poorly understood. We identified a small cluster of patients in Brazil who experienced 2 episodes of coronavirus disease (COVID-19) in March and late May 2020. In the first episode, patients manifested an enhanced innate response compared with healthy persons, but neutralizing humoral immunity was not fully achieved. The second episode was associated with different SARS-CoV-2 strains, higher viral loads, and clinical symptoms. Our finding that persons with mild COVID-19 may have controlled SARS-CoV-2 replication without developing detectable humoral immunity suggests that reinfection is more frequent than supposed, but this hypothesis is not well documented.

In vitro antiviral activity of the anti-HCV drugs daclatasvir and sofosbuvir against SARS-CoV-2, the aetiological agent of COVID-19.

BACKGROUND: Current approaches of drug repurposing against COVID-19 have not proven overwhelmingly successful and the SARS-CoV-2 pandemic continues to cause major global mortality. SARS-CoV-2 nsp12, its RNA polymerase, shares homology in the nucleotide uptake channel with the HCV orthologue enzyme NS5B. Besides, HCV enzyme NS5A has pleiotropic activities, such as RNA binding, that are shared with various SARS-CoV-2 proteins. Thus, anti-HCV NS5B and NS5A inhibitors, like sofosbuvir and daclatasvir, respectively, could be endowed with anti-SARS-CoV-2 activity. METHODS: SARS-CoV-2-infected Vero cells, HuH-7 cells, Calu-3 cells, neural stem cells and monocytes were used to investigate the effects of daclatasvir and sofosbuvir. In silico and cell-free based assays were performed with SARS-CoV-2 RNA and nsp12 to better comprehend the mechanism of inhibition of the investigated compounds. A physiologically based pharmacokinetic model was generated to estimate daclatasvir's dose and schedule to maximize the probability of success for COVID-19. RESULTS: Daclatasvir inhibited SARS-CoV-2 replication in Vero, HuH-7 and Calu-3 cells, with potencies of 0.8, 0.6 and 1.1 µM, respectively. Although less potent than daclatasvir, sofosbuvir alone and combined with daclatasvir inhibited replication in Calu-3 cells. Sofosbuvir and daclatasvir prevented virus-induced neuronal apoptosis and release of cytokine storm-related inflammatory mediators, respectively. Sofosbuvir inhibited RNA synthesis by chain termination and daclatasvir targeted the folding of secondary RNA structures in the SARS-CoV-2 genome. Concentrations required for partial daclatasvir in vitro activity are achieved in plasma at Cmax after administration of the approved dose to humans. CONCLUSIONS: Daclatasvir, alone or in combination with sofosbuvir, at higher doses than used against HCV, may be further fostered as an anti-COVID-19 therapy.

Endoplasmic reticulum stress as the basis of obesity and metabolic diseases: focus on adipose tissue, liver, and pancreas.

Obesity challenges lipid and carbohydrate metabolism. The resulting glucolipotoxicity  causes endoplasmic reticulum (ER) dysfunction, provoking the accumulation of immature proteins, which triggers the unfolded protein reaction (UPR) as an attempt to reestablish ER homeostasis. When the three branches of UPR fail to correct the unfolded/misfolded proteins, ER stress happens. Excessive dietary saturated fatty acids or fructose exhibit the same impact on the ER stress, induced by excessive ectopic fat accumulation or rising blood glucose levels, and meta-inflammation. These metabolic abnormalities can alleviate through dietary interventions. Many pathways are disrupted in adipose tissue, liver, and pancreas during ER stress, compromising browning and thermogenesis, favoring hepatic lipogenesis, and impairing glucose-stimulated insulin secretion within pancreatic beta cells. As a result, ER stress takes part in obesity, hepatic steatosis, and diabetes pathogenesis, arising as a potential target to treat or even prevent metabolic diseases. The scientific community seeks strategies to alleviate ER stress by avoiding inflammation, apoptosis, lipogenesis suppression, and insulin sensitivity augmentation through pharmacological and non-pharmacological interventions. This comprehensive review aimed to describe the contribution of excessive dietary fat or sugar to ER stress and the impact of this adverse cellular environment on adipose tissue, liver, and pancreas function.

Ilex paraguariensis extract provides increased resistance against oxidative stress and protection against Amyloid beta-induced toxicity compared to caffeine in Caenorhabditis elegans.

Ilex paraguariensis is a plant from South America, used to prepare a tea-like beverage rich in caffeine and polyphenols with antioxidant proprieties. Caffeine consumption is associated with a lower risk of age-associated neuropathologies, besides several extracts that have antioxidant proprieties are known to be neuroprotective, and oxidative stress strongly correlates with Aß-toxicity. This study aims to investigate the neuroprotective effects of the Ilex paraguariensis hydroalcoholic extract (IPHE) and to evaluate if caffeine agent present in IPHE exerts neuroprotective effects in an amyloid beta-peptide (Aß)-induced toxicity in Caenorhabditis elegans. The wild-type and CL2006 worms were treated with IPHE (2 and 4 mg/mL) or caffeine (200 and 400 µM) since larval stage 1 (L1) until they achieved the required age for each assay. IPHE and caffeine increased the lifespan and appeared to act directly by reactive oxygen species (ROS) scavenger in both wild-type and CL2006 worms, also conferred resistance against oxidative stress in wild-type animals. Furthermore, both treatments delayed Aß-induced paralysis and decreased AChE activity in CL2006. The protective effect of IPHE against Aß-induced paralysis was found to be dependent on heat shock factor hsf-1 and FOXO-family transcription factor daf-16, which are respectively involved in aging-related processes and chaperone synthesis, while that of caffeine was dependent only on daf-16. Mechanistically, IPHE and caffeine decreased the levels of Aß mRNA in the CL2006 worms; however, only IPHE induced expression of the heat shock chaperonin hsp-16.2, involved in protein homeostasis. The results were overall better when treated with IPHE than with caffeine.

The use of photobiomodulation therapy or LED and mineral trioxide aggregate improves the repair of complete tibial fractures treated with wire osteosynthesis in rodents.

The repair of large bone defects is lengthy and complex. Both biomaterials and phototherapy have been used to improve bone repair. We aimed to describe histologically the repair of tibial fractures treated by wiring (W), irradiated or not, with laser (λ780 nm, 70 mW, CW, spot area of 0.5 cm2, 20.4 J/cm2 (4 × 5.1 J/cm2, Twin Flex Evolution®, MM Optics, Sao Carlos, SP, Brazil) per session, 300 s, 142.8 J/cm2 per treatment) or LED (λ850 ± 10 nm, 150 mW, spot area of 0.5 cm2, 20.4 J/cm2 per session, 64 s, 142.8 J/cm2 per treatment, Fisioled®, MM Optics, Sao Carlos, Sao Paulo, Brazil) and associated or not to the use of mineral trioxide aggregate (MTA, Angelus®, Londrina, PR, Brazil). Inflammation was discrete on groups W and W + LEDPT and absent on the others. Phototherapy protocols started immediately before suturing and repeated at every other day for 15 days. Collagen deposition intense on groups W + LEDPT, W + BIO-MTA + LaserPT and W + BIO-MTA + LEDPT and discrete or moderate on the other groups. Reabsorption was discrete on groups W and W + LEDPT and absent on the other groups. Neoformation varied greatly between groups. Most groups were partial and moderately filed with new-formed bone (W, W + LaserPT, W + LEDPT, W + BIO-MTA + LEDPT). On groups W + BIO-MTA and W + BIO-MTA + LaserPT bone, neoformation was intense and complete. Our results are indicative that the association of MTA and PBMT (λ = 780 nm) improves the repair of complete tibial fracture treated with wire osteosynthesis in a rodent model more efficiently than LED (λ = 850 ± 10 nm).