Thermal treatment under oxidative conditions increases the antioxidant and antiglycation activity of Chilean Tórtola beans (Phaseolus vulgaris).

The influence of oxygen on the thermal treatment (TT) of secondary metabolite-enriched extracts (SMEEs) from Tórtola beans and procyanidin C1 (PC1) on the inhibition of advanced glycation end products (AGEs) generation in proteins was investigated. SMEE was incubated at 4 °C (control) or thermally treated at 60 °C for 2 h, at either 0 % O2 (I) or 20 % O2 (II). Treatments I and II increased the content of procyanidin dimers B2. Treatment II was more effective than the control or treatment I in preventing homocysteine oxidation and AGEs generation. TT of PC1 at 0 % or 20 % O2 generated procyanidin dimers and tetramers. PC1 TT at 20 % O2 exhibited higher oxidation potentials and lower IC50 values of fluorescent AGEs than those of controls or TT at 0 % O2. These findings indicate that SMEE from Tórtola beans after treatment II changes the degree of polymerization and oxidation procyanidins, thereby increasing their antiglycation activity.

Evaluating sacha inchi (Plukenetia volubilis) oil stability and physicochemical properties: A comparison between conventional extraction and supercritical fluids.

This study aimed to compare the effects of two extraction techniques (conventional n-hexane and supercritical CO2) on the oil extraction yields, fatty acids profile, anti-hyaluronidase activity, oxidative stability, and in vitro bioactivities of oils from Sacha Inchi (Plukenetia volubilis). Higher oil extraction yield (99 %) was achieved using the SC-CO2, although similar fatty acids profiles were depicted between both treatments (p < 0.05). The SC-CO2 oil presented higher anti-hyaluronidase (31 %) activity, but lower oxidative stability (5.05 h) compared to the solvent extraction (10 %, and 5.3 h, respectively). In vitro assays further revealed that the best human normal colon cells (FHC) cell viability (100 %), anti-inflammatory (50 % lower NO production), and antioxidant (20 % ROS reduction) activities were consistently observed in both extraction treatments at concentrations of 50 µg/mL and higher. These findings highlight the potential of supercritical CO2 extraction in yielding Sacha Inchi oil with enhanced bioactive properties without the disadvantages of the use of organic solvents extraction.

Enhancing apple postharvest protection: Efficacy of pectin coatings containing Cryptococcus laurentii against Penicillium expansum.

The aim of this work is the application of pectin coatings containing Cryptococcus laurentii as a method of biocontrol of Penicillium expansum for postharvest protection of apples. For this purpose, the yeast was incorporated into a pectin matrix, and its viability and biocontrol activity in vitro and in vivo against P. expansum was evaluated over time. In addition, the influence of the sterilization process on coating thickness was studied. Results showed that pectin coating with C. laurentii enhanced mycelial growth inhibition in vitro studies, while no significant differences were observed in disease incidence and severity reduction in vivo studies. The sterilization process reduced the viscosity of the pectin solution, resulting in coating thicknesses ranging from 0.5 to 1 µm. As a general evaluation, in vitro and in vivo, biocontrol assays were useful in demonstrating better postharvest protection of the yeast at 7 °C concerning 25 °C.

Assessing the potential fasting and postprandial mechanisms involved in the acute hypoglycemic and anti-hyperglycemic effects of four selected plants from Iran used in traditional Persian medicine.

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Persian medicine (TPM), people often use herbal infusions as a dosage form to treat diseases related to hyperglycemia, known as 'dam-kardeh'. Traditionally, herbal preparations of Eryngium bungei Boiss. (E. b), Tragopogon buphthalmoides (DC.) Boiss. (T. b), Salvia hydrangea DC. ex Benth. (S. h), and Juniperus polycarpos K. Koch. (J. p) are used to manage diabetes in Iran. However, there is no evidence of their effectiveness in controlling glucose levels and their mechanisms remain unclear. AIM OF THE STUDY: This study aimed to investigate whether traditional doses of plant infusions can have hypoglycemic and/or anti-hyperglycemic effects during fasting and/or postprandial states and establish the basis for future research on their potential mechanisms of action. MATERIALS AND METHODS: The effects of traditional doses of herbal extracts on blood glucose levels in STZ-NA-induced hyperglycemic rats were investigated in 2-h acute tests during fasting and postprandial states (with a glucose load). In addition, the potential inhibitory effect in vitro of enzymes involved in relevant pathways, such as gluconeogenesis (fructose-1,6-bisphosphatase, FBPase and glucose-6-phosphatase, G6Pase), carbohydrate breakdown (intestinal α-glucosidases), and insulin sensitivity (protein tyrosine phosphatase 1B, PTP-1B) was evaluated. Acute toxicity tests were carried out and HPLC-SQ-TOF was used to analyze the chemical profiles of the plant extracts. RESULTS: In the fasting state, T. b, S. h, and E. b were as effective as glibenclamide in lowering blood glucose levels in hyperglycemic rats. Moreover, all three suppressed G6Pase and FBPase enzymatic activity by 90-97% and 80-91%, respectively. On the other hand, significant postprandial hypoglycemic efficacy was observed for E. b, S. h, and T. b. Based on the AUC values, T. b caused a reduction comparable to the therapeutic efficacy of repaglinide. When investigating the possible mechanisms of action involved in this activity, E. b, S. h, and T. b showed significant inhibition of PTP-1B in vitro (>70%). Finally, all plant extracts showed no signs of acute toxicity. Several compounds that may contribute to biological activities were identified, including phenolic acids and flavonoid glycosides. CONCLUSIONS: The present study supports the traditional use of T. b, E. b and S. h for the control of diabetes in the fasting and postprandial state. Moreover, these plants were found to be rich in bioactive compounds with hypoglycemic and antihyperglycemic activities. On the other hand, J. p, showed a modest effect only in the fasting state and after 90 min. Further studies are needed to expand these results by analyzing the chemical composition and using complementary experimental models.

Alkaloids solenopsins from fire ants display in vitro and in vivo activity against the yeast Candida auris.

The urgency surrounding Candida auris as a public health threat is highlighted by both the Center for Disease Control (CDC) and World Health Organization (WHO) that categorized this species as a priority fungal pathogen. Given the current limitations of antifungal therapy for C. auris, particularly due to its multiple resistance to the current antifungals, the identification of new drugs is of paramount importance. Some alkaloids abundant in the venom of the red invasive fire ant (Solenopsis invicta), known as solenopsins, have garnered attention as potent inhibitors of bacterial biofilms, and there are no studies demonstrating such effects against fungal pathogens. Thus, we herein investigated the antibiotic efficacy of solenopsin alkaloids against C. auris biofilms and planktonic cells. Both natural and synthetic solenopsins inhibited the growth of C. auris strains from different clades, including fluconazole and amphotericin B-resistant isolates. Such alkaloids also inhibited matrix deposition and altered cellular metabolic activity of C. auris in biofilm conditions. Mechanistically, the alkaloids compromised membrane integrity as measured by propidium iodide uptake in exposed planktonic cells. Additionally, combining the alkaloids with AMB yielded an additive antifungal effect, even against AMB-resistant strains. Finally, both extracted solenopsins and the synthetic analogues demonstrated protective effect in vivo against C. auris infection in the invertebrate model Galleria mellonella. These findings underscore the potent antifungal activities of solenopsins against C. auris and suggest their inclusion in future drug development. Furthermore, exploring derivatives of solenopsins could reveal novel compounds with therapeutic promise.

The ethanolic extract of Gomphrena celosioides is not carcinogenic and has antigenotoxic effects and chemopreventive Properties.

Gomphrena celosioides, popularly known as perpétua, perpétua brava, bachelor´s button and prostate globe amarahth, is used for the treatment of urinary tract disorders, kidney stones, for skin diseases, infectious diseases, gastrointestinal and respiratory conditions. Rich in phenolic acids and flavonoids, this plant has therefore a potential for use in cancer prevention. Given the above, the present research aimed to evaluate the carcinogenic effect of the ethanolic extract of G. celosioides (EEGc) in an alternative model of Drosophila melanogaster and the genotoxic and antigenotoxic effects in Swiss mice. The larval survival test and the detection of epithelial tumor clones were performed in D. melanogaster. The tested EEGc concentrations were 0.96, 1.92, 3.85 and 7.70 mg/mL. In Swiss mice, the genotoxicity and antigenotoxicity of doses of 100, 1,000 and 2,000 mg/Kg were evaluated. The results showed that EEGc at a concentration of 7.70 mg/mL reduced (p<0.05) larval survival. However, EEGc was not carcinogenic, and the lowest concentration (0.96 mg/mL) prevented (p<0.05) the basal occurrence of epithelial tumors. In mice, EEGc at the highest dose (2,000mg/Kg) increased the frequency of genomic lesions (p<0.05). Yet, none of the doses caused chromosomal lesions (p>0.05). When associated with cyclophosphamide, EEGc was antigenotoxic (p<0.05). The percentages of reduction of genomic damage ranged from 33.39 to 63.23% and of chromosomal damage from 20.00 to 77.19%. In view of the above, it is suggested that EEGc is not carcinogenic, has an antigenotoxic effect and chemopreventive properties.

AmpClass: an Antimicrobial Peptide Predictor Based on Supervised Machine Learning.

In the last decades, antibiotic resistance has been considered a severe problem worldwide. Antimicrobial peptides (AMPs) are molecules that have shown potential for the development of new drugs against antibiotic-resistant bacteria. Nowadays, medicinal drug researchers use supervised learning methods to screen new peptides with antimicrobial potency to save time and resources. In this work, we consolidate a database with 15945 AMPs and 12535 non-AMPs taken as the base to train a pool of supervised learning models to recognize peptides with antimicrobial activity. Results show that the proposed tool (AmpClass) outperforms classical state-of-the-art prediction models and achieves similar results compared with deep learning models.

Plant phytochemicals-mediated synthesis of zinc oxide nanoparticles with antimicrobial, pharmacological, and environmental applications.

Nanotechnology is a fast-growing field with large number of applications. Therefore, the current study, was designed to prepare Zinc Oxide nanoparticles (ZnO NPs) from A. modesta leaves extract through a cost-effective method. The prepared NPs were characterized through UV-Vis Spectroscopy (UV-Vis), Dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction analysis (XRD), scanning electron microscope (SEM), and energy dispersive X-ray (EDX). The XRD and DLS analysis revealed the hexagonal nanocrystalline nature of ZnO NPs. The FTIR results displayed multiple fictional groups and UV results confirmed its optical properties. The average size of the NPs was 68.3 nm with a band gap of 2.71 eV. The SEM images divulge a clover leaf shape of ZnO NPs. The EDX spectrum revealed the presence of zinc and oxygen. The prepared NPs showed excellent biomedical application. The highest antileishmanial activity was 68%, anti-inflammatory activity was 78%, total antioxidant capacity (TAC) was 79.1%, antibacterial potential (ZOI) 22.1 mm, and highest growth inhibition of 85 ± 2.1% against A. rabiei. The adsorption efficiency of 85.3% within 120 min was obtained. Conclusively ZnO NPs have shown potential biomedical and environmental applications and ought to be the more investigated to enhance their practical use.

Post-natal antibiotic exposure in mother rat (F0) induces anxiety like behavior in adult rat offspring (F1) by activating HPA axis and down-regulating the Nr3c1 gene.

Early postnatal administration of antibiotics has been linked to lasting effects on brain development and behavior. Research conducted on animals that are free from germs has demonstrated that the impact of microbiome colonization on the regulation of the hypothalamic-pituitary-adrenal (HPA) axis and neuroendocrine pathways is substantial, which play a crucial role in stress management. Nevertheless, it is still uncertain if the exposure to antibiotics in rat dams (F0-generation) before weaning is associated with neurobehavioral changes in rat offspring (F1-generation) during adulthood. In order to investigate the effects, we perturbed the intestinal microbiota of rat dams (F0 generation) by administering cefixime (CEF), an antibiotic commonly used for obstetric purposes, at clinically relevant doses (1 mg/kg, 2.5 mg/kg or 5 mg/kg). Anxiety-like behaviors in adult offspring was evaluated through the utilization of elevated plus maze (EPM) and open field paradigm (OFP) following a six-week interval from birth (PND42). Subsequent to behavioral assessments, the rats were euthanized, and their brains and blood was collected for biochemical analysis. Plasma corticosterone concentration was used to assess HPA activity, whereas the quantitative real-time polymerase chain reaction (PCR) was employed to determine the transcription levels of the glucocorticoid receptor (GR) Nr3c1. The offspring of F1 that were administered antibiotics before being weaned spent less time in the EPM open arm. The alterations were accompanied by increased levels of corticosterone in the bloodstream. The gene expression study revealed a decrease in the levels of mRNA transcription of Nr3c1. This research emphasizes the possible long-term effects of antibiotic exposure before weaning on the development of anxiety in offspring upon adulthood.

Long­term effects of vitexin against development of pentylenetetrazole­induced kindling in rats.

Evidence is provided that the glycosylated flavonoid vitexin (apigenin­8­C­beta­D­glucopyranoside) attenuates pentylenetetrazole (PTZ)­induced acute tonic­clonic seizures in rats. However, the effects of chronic and systemic vitexin in PTZ­kindled rats remain unknown. The aim of this work was to investigate the effect of long­term treatment with vitexin in the PTZ­kindling model of epilepsy. Male Wistar rats received intraperitoneal injections of PTZ at a subconvulsive dose of 35 mg/kg every other day for 29 days. Either saline containing dimethyl sulfoxide - DMSO 1%  (vehicle), diazepam (2 mg/kg; positive control) or vitexin (2.5 mg/kg) was administered intraperitoneally 30 min before each PTZ injection. The behavioral reactions were recorded by 30 min immediately after each PTZ injection. Furthermore, on the 31st day, that is, 48 h after the latter dose of PTZ, the animals were euthanized and renal and hepatic biochemical markers were evaluated in blood serum. Chronic treatment with either diazepam or vitexin attenuated the seizures provoked by PTZ injections. Neither diazepam nor vitexin caused changes in renal levels of creatinine and urea and in hepatic levels of aspartate aminotransferase and alanine aminotransferase. Our findings suggest that chronic administration of vitexin attenuates the progression of PTZ­induced kindling without causing side effects on kidneys and liver.

Effect of the Application of PGF2α Associated With Ovulation Induction in a Fixed-Time Superovulation Programme for Precocious Nellore Heifers.

This study evaluated the effect of prostaglandin F2α (PGF2α) associated with gonadotropin-releasing hormone (GnRH) for ovulation induction in precocious indicus heifers submitted to a fixed-time superovulation (SOV) programme. Precocious Nellore heifers (n = 35), aged 13 months, were subjected to the SOV protocol. On day 0 (D0), all animals received intravaginal insertion of a progesterone (P4) device along with intramuscular administration of 2 mg of oestradiol benzoate, plus 200 IU of follicle-stimulating hormone in decreasing doses, with 12-h intervals between D4 and D7, in addition to 150 µg of D-cloprostenol on D6 and device removal on D7. On D8, the donors received 10.5 µg of buserelin acetate and the treatment group received 300 µg of D-cloprostenol/PGF2α. Artificial insemination was performed 12 h and 24 h after GnRH administration using frozen semen. On D15 of the protocol (i.e., D7 after insemination), the embryos were collected and evaluated. All animals passed through the control and treatment groups. Results were evaluated by analysis of variance using an adjusted mixed-effects model (p < 0.05). There was no difference in the total number of embryos between the control and treatment groups (10.40 ± 1.52 vs. 9.60 ± 1.36; p = 0.63) or viable embryos (6.30 ± 1.22 vs. 4.30 ± 0.71). For precocious indicus heifers, treatment with PGF2α in association with GnRH did not affect embryo production in the fixed-time SOV protocol.

Tissue response in a rat model of denture stomatitis treated with tissue conditioner containing antifungal complexed with ß-cyclodextrin.

Introduction. Tissue conditioners modified with antifungals are a potential alternative to denture stomatitis (DS) treatment.Gap Statement. Information on tissue response to this treatment before its clinical application is lacking.Aim. This study aimed to evaluate the tissue response of a tissue conditioner modified with antifungals in a rat model of DS.Methodology. After DS induction for 4 days under antibiotic therapy, Wistar rats had their intraoral devices (IODs) relined with the tissue conditioner Softone without (Soft) or with the MICs against Candida albicans of nystatin (Nys) or chlorhexidine (Chx) complexed or not with ß-cyclodextrin (Nys:ßCD and Chx:ßCD). Three controls were included: healthy rats [negative control (Nc)], rats using a sterile IOD [sterile device (Sd)] and rats with DS that did not receive treatment (DS). After 4 days of treatment, the palatal mucosa under the IODs underwent histological processing for morphohistopathological and histometric analyses, morphology of collagen fibres (birefringence), immunohistochemistry for the expression of cell proliferation (proliferating cell nuclear antigen) and cytokine (IL-1ß).Results. The Nc and Sd groups were similar (P>0.05), displaying epithelial and connective tissues without any discernible changes in the parameters assessed. The DS and Soft groups exhibited pronounced epithelial alterations, cell proliferation and expression of the cytokine IL-1ß. In groups treated with drug incorporation (Nys, Chx, Nys:ßCD and Chx:ßCD), all samples demonstrated a reduction in tissue inflammation or complete tissue recovery, with an epithelium compatible with health. For the immunohistochemical parameters, the Chx, Nys:ßCD and Chx:ßCD groups were comparable with Nc (P>0.05).Conclusion. The proposed treatment could be promising for DS, as it led to the tissue recovery of the palatal mucosa. Nevertheless, much lower concentrations of complexed antifungals were required to achieve a similar or higher degree of tissue response compared with uncomplexed drugs in a modified tissue conditioner formulation.

Intriguing hepatoprotective effects of sucrose on hepatocellular carcinoma pathogenesis.

Chronic liver disease is closely linked to dietary intake factors, such as high consumption of simple carbohydrates including sucrose. In this study, the influence of sucrose on the development of hepatocellular carcinoma (HCC), the most common primary liver malignancy, was explored. Using the hepatocarcinogen diethylnitrosamine (DEN) to induce HCC in the rat, we co-administered sucrose with DEN. The co-administration significantly modified body, liver and pancreas weight, as well as, serum fatty acids and triglycerides. DEN caused liver structural alteration, fibrosis, and tumor formation; surprisingly, co-administration with sucrose restored hepatic lipids, improved liver architecture, and reduced fibrosis and tumor development. Sucrose intake negatively regulated tumor markers and cell proliferation, and reduced the expression of genes associated with lipid metabolism and oxidative stress response. These findings highlight a hepatoprotective effect of sucrose during DEN-induced hepatocarcinogenesis, underlining an intriguing role of high sucrose consumption during HCC development and providing new insights as well as possible pathways of cellular protection under sucrose intake on hepatocarcinogenesis.

Traditional Medicine, Culture, and Psychedelic Science: New Pathways for Recovery From Substance Use Disorders.

OBJECTIVE: This article provides an intercultural transdisciplinary perspective on the Indigenous roots of the resurging field of psychedelic science in the management of substance use disorders (SUDs). Ritual uses of entheogens (i.e., psychedelics of natural origin) are elaborate technologies for navigating, containing, and therapeutically directing non-ordinary states of consciousness induced by these compounds. METHOD: A narrative review of the literature on the therapeutic potential of ayahuasca, peyote, psilocybin-containing mushrooms, Incilius alvarius-derived 5-MeO-DMT (5-methoxy-N,N-dimethyltryptamine), and iboga for the treatment of SUDs was conducted. This article also describes the application of some of these entheogens within a pilot intercultural clinical program implemented by the Yaqui tribe in Sonora, Mexico, for the treatment of SUDs and other mental health challenges. RESULTS: Observational research and preliminary clinical studies indicate the therapeutic potential and relative safety of these compounds in appropriate contexts, including the use of careful screening practices and complementary psychotherapeutic interventions. CONCLUSIONS: Preliminary research points to the potential therapeutic value of integrating entheogenic plant and fungi medicine with culturally attuned therapeutic strategies. Respectful intercultural dialogue across worldviews and scientific paradigms allows for the further development of new perspectives at the intersection of entheogens, addiction treatment, mental health, and traditional medicine. More interdisciplinary research is necessary in this field.

Pneumococcal surface protein A (PspA) prevents killing of Streptococcus pneumoniae by indolicidin.

Pneumococcal surface protein A (PspA) is an important virulence factor in Streptococcus pneumoniae that binds to lactoferrin and protects the bacterium from the bactericidal action of lactoferricins-cationic peptides released upon lactoferrin proteolysis. The present study investigated if PspA can prevent killing by another cationic peptide, indolicidin. PspA-negative pneumococci were more sensitive to indolicidin-induced killing than bacteria expressing PspA, suggesting that PspA prevents the bactericidal action of indolicidin. Similarly, chemical removal of choline-binding proteins increased sensitivity to indolicidin. The absence of capsule and PspA had an additive effect on pneumococcal killing by the AMP. Furthermore, anti-PspA antibodies enhanced the bactericidal effect of indolicidin on pneumococci, while addition of soluble PspA fragments competitively inhibited indolicidin action. Previous in silico analysis suggests a possible interaction between PspA and indolicidin. Thus, we hypothesize that PspA acts by sequestering indolicidin and preventing it from reaching the bacterial membrane. A specific interaction between PspA and indolicidin was demonstrated by mass spectrometry, confirming that PspA can actively bind to the AMP. These results reinforce the vaccine potential of PspA and suggest a possible mechanism of innate immune evasion employed by pneumococci, which involves binding to cationic peptides and hindering their ability to damage the bacterial membranes.

Amelioration of nephrotoxicity by targeting ferroptosis: role of NCOA4, IREB2, and SLC7a11 signaling.

Nephrotoxicity is a common complication that limits the clinical utility of cisplatin. Ferroptosis is an iron-dependent necrotic cell death program that is mediated by phospholipid peroxidation. The molecular mechanisms that disrupt iron homeostasis and lead to ferroptosis are yet to be elucidated. In this study, we aimed to investigate the involvement of nuclear receptor coactivator 4 (NCOA4), a selective cargo receptor that mediates ferroptosis and autophagic degradation of ferritin in nephrotoxicity. Adult male Sprague-Dawley rats were randomly-assigned to four groups: control group, cisplatin (Cis)-treated group, deferiprone (DEF)-treated group, and Cis+DEF co-treated group. Serum, urine, and kidneys were isolated to perform biochemical, morphometric, and immunohistochemical analysis. Iron accumulation was found to predispose to ferroptotic damage of the renal tubular cells. Treatment with deferiprone highlights the role of ferroptosis in nephrotoxicity. Upregulation of NCOA4 in parallel with low ferritin level in renal tissue seems to participate in iron-induced ferroptosis. This study indicated that ferroptosis may participate in cisplatin-induced tubular cell death and nephrotoxicity through iron-mediated lipid peroxidation. Iron dyshomeostasis could be attributed to NCOA4-mediated ferritin degradation.

Osteogenic mechanism of deciduous teeth periodontal ligament stem cells in inflammatory environment.

This study aimed to illustrate the biological behavior and changes in cell function during the progression of apical periodontitis in deciduous teeth and to explore the underlying molecular mechanism. Deciduous teeth periodontal ligament stem cells (DePDLSCs) were derived and their identity was confirmed. The viability, inflammation, and osteogenic ability of cells were tested by exposing them to various concentrations of lipopolysaccharide (LPS) (0-100 µg/mL) using the cell counting kit-8 (CCK-8) assay, reverse transcription polymerase chain reaction (real-time PCR), alkaline phosphatase (ALP) staining, and ALP activity assay. In addition, osteogenic-induced cells with and without 10 µg/mL LPS were harvested for high-throughput sequencing. Based on sequencing data, proinflammatory factors and ALP expression were measured after interference with the PI3K-AKT signaling pathway activator, 740Y-P. LPS biphasically affected the proliferation and osteogenesis of DePDLSCs. Low concentrations of LPS showed stimulatory effects, whereas inhibitory effects were observed at high concentrations. Sequencing analysis showed that the PI3K-AKT signaling pathway was significantly downregulated when DePDLSCs were treated with 10 µg/mL LPS. The LPS-induced inflammation and osteogenesis inhibition of DePDLSCs were partially rescued by 740Y-P treatment. In conclusion, LPS affected DePDLSCs proliferation and osteogenesis in a biphasic manner. Moderate activation of PI3K-AKT signaling pathway was beneficial for osteogenic differentiation and anti-inflammatory effect in DePDLSCs. This research may provide etiological probes for apical periodontitis and its treatment.

Synergistic effect of venetoclax and ibrutinib on ibrutinib-resistant ABC-type DLBCL cells.

Despite the widespread use of R-CHOP therapy in diffuse large B-cell lymphoma (DLBCL), the therapeutic efficacy for this disease remains suboptimal, primarily due to the heterogeneity of refractory and/or relapsed diseases. To address this challenge, optimization of DLBCL treatment regimens has focused on the strategy of combining an additional drug "X" with R-CHOP to enhance efficacy. However, the failure of R-CHOP combined with the BTK inhibitor ibrutinib in treating ABC-type DLBCL patients has raised significant concerns regarding ibrutinib resistance. While some studies suggest that venetoclax may synergize with ibrutinib to kill ibrutinib-resistant cells, the underlying mechanisms remain unclear. Our study aimed to validate the enhanced tumor-suppressive effect of combining ibrutinib with venetoclax against ibrutinib-resistant cells and elucidate its potential mechanisms. Our experimental results demonstrated that ibrutinib-resistant cells exhibited significant cytotoxicity to the combination therapy of ibrutinib and venetoclax, inducing cell apoptosis through activation of the mitochondrial pathway and inhibition of aerobic respiration. Furthermore, we validated the inhibitory effect of this combination therapy on tumor growth in in vivo models. Therefore, our study proposes that the combination therapy of ibrutinib and venetoclax is a promising treatment strategy that can be applied in clinical practice for ABC-type DLBCL, offering a new solution to overcome the urgent challenge of ibrutinib resistance.

Influence of vitamin D on muscle strength and botulinum toxin dosage through surface electromyography.

PURPOSE: To evaluate the influence of patients' serum vitamin D levels on muscle strength characteristics and whether it impacts the durability of botulinum toxin (BT) treatment. METHODS: The muscle strength of the frontal and corrugator muscles was evaluated before and after the application of TB with pre- and post-application control measurements, and at weeks 2, 5 and 12. The effect of vitamin D on muscle strength and its interaction with BT were investigated in 20 patients. The muscle contraction force was measured by surface electromyography. RESULTS: The results revealed statistically significant differences between the frontal measurement groups at weeks 2 and 5, as well as for the corrugator in the same weeks and at week 12. Regarding vitamin D, significant differences were observed only in the initial group with vitamin D > 30 ng/mL compared to < 30 ng/mL for the frontal muscles. Patients with higher levels of vitamin D had higher average muscle strength compared to those with lower levels in all evaluations. CONCLUSIONS: It was observed that vitamin D influences muscle strength and the necessary dosage of BT.

Effects of ozone therapy applied topically, by bagging, or both on the healing of clean wounds induced in rat's skin.

PURPOSE: This study aimed to evaluate the effects of ozone therapy applied topically and/or by bagging on the healing of clean wounds induced in rat's skin. METHODS: One hundred and twenty male rats of about 16 weeks old was divided into five groups: G1) saline solution (0.9%); G2) sunflower oil; G3) ozonated sunflower oil; G4) ozone bagging; G5) association of ozonated sunflower oil and ozone bagging. The wounds were evaluated through macroscopic, morphometric, histopathologic, and tensile strength analyses. RESULTS: Analysis among groups showed a lower percentage of wound contraction in G1 compared to G4 only in M7D. The tensile strength of the wounds showed differences among groups in the seventh (M7D) and the 14th (M14D) postoperative day, and among time points in G1 (M14D > M7D). The elongation of the wounds showed differences in G3 (M7D > M14D). Histological evaluation of the wounds showed significant change in bleeding, mixed to mononuclear infiltrate, congestion, and tissue disorganization for tissue organization between groups and time points. CONCLUSIONS: Ozone therapy applied topically and/or by bagging was not deleterious to the healing of clean wounds induced in rat's skin, but ozone bagging showed the best contribution to the healing process.