Safety profile and effects on the peripheral immune response of fecal microbiota transplantation in clinically healthy dogs.

BACKGROUND: Fecal microbiota transplantation (FMT) is increasingly used for gastrointestinal and extra-gastrointestinal diseases in veterinary medicine. However, its effects on immune responses and possible adverse events have not been systematically investigated. HYPOTHESIS/OBJECTIVES: Determine the short-term safety profile and changes in the peripheral immune system after a single FMT administration in healthy dogs. ANIMALS: Ten client-owned, clinically healthy dogs as FMT recipients, and 2 client-owned clinically healthy dogs as FMT donors. METHODS: Prospective non-randomized clinical trial. A single rectal enema of 5 g/kg was given to clinically healthy canine recipients. During the 28 days after FMT administration, owners self-reported adverse events and fecal scores. On Days 0 (baseline), 1, 4, 10, and 28 after FMT, fecal and blood samples were collected. The canine fecal dysbiosis index (DI) was calculated using qPCR. RESULTS: No significant changes were found in the following variables: CBC, serum biochemistry, C-reactive protein, serum cytokines (interleukins [IL]-2, -6, -8, tumor necrosis factor [TNF]-α), peripheral leukocytes (B cells, T cells, cluster of differentiation [CD]4+ T cells, CD8+ T cells, T regulatory cells), and the canine DI. Mild vomiting (n = 3), diarrhea (n = 4), decreased activity (n = 2), and inappetence (n = 1) were reported, and resolved without intervention. CONCLUSIONS AND CLINICAL IMPORTANCE: Fecal microbiota transplantation did not significantly alter the evaluated variables and recipients experienced minimal adverse events associated with FMT administration. Fecal microbiota transplantation was not associated with serious adverse events, changes in peripheral immunologic variables, or the canine DI in the short-term.

Regulation of Gut Microbiota by Herbal Medicines.

Preserving host health and homeostasis is largely dependent on the human gut microbiome, a varied and ever-changing population of bacteria living in the gastrointestinal tract. This article aims to explore the multifaceted functions of the gut microbiome and shed light on the evolving field of research investigating the impact of herbal medicines on both the composition and functionality of the gut microbiome. Through a comprehensive overview, we aim to provide insights into the intricate relationship between herbal remedies and the gut microbiome, fostering a better understanding of their potential implications for human health.The gut microbiota is composed of trillions of microorganisms, predominantly bacteria, but also viruses, fungi, and archaea. It functions as a complex ecosystem that interacts with the host in various ways. It aids in nutrient metabolism, modulates the immune system, provides protection against pathogens, and influences host physiology. Moreover, it has been linked to a range of health outcomes, including digestion, metabolic health, and even mental well-being. Recent research has shed light on the potential of herbal medicines to modulate the gut microbiome. Herbal medicines, derived from plants and often used in traditional medicine systems, contain a diverse array of phytochemicals, which can directly or indirectly impact gut microbial composition. These phytochemicals can either act as prebiotics, promoting the growth of beneficial bacteria, or possess antimicrobial properties, targeting harmful pathogens. Several studies have demonstrated the effects of specific herbal medicines on the gut microbiome. For example, extracts from herbs have been shown to enhance the abundance of beneficial bacteria, such as Bifidobacterium and Lactobacillus, while reducing potentially harmful microbes. Moreover, herbal medicines have exhibited promising antimicrobial effects against certain pathogenic bacteria. The modulation of the gut microbiome by herbal medicines has potential therapeutic implications. Research suggests herbal interventions could be harnessed to alleviate gastrointestinal disorders, support immune function, and even impact metabolic health. However, it is important to note that individual responses to herbal treatments can vary due to genetics, diet, and baseline microbiome composition. In conclusion, the gut microbiome is a critical player in maintaining human health, and its modulation by herbal medicines is a burgeoning area of research. Understanding the complex interactions between herbal compounds and gut microbiota will pave the way for innovative approaches to personalized healthcare and the development of herbal-based therapeutics aimed at promoting gut health and overall well-being.

Glycolysis-non-canonical glutamine dual-metabolism regulation nanodrug enhanced the phototherapy effect for pancreatic ductal adenocarcinoma treatment.

Clinical pancreatic ductal adenocarcinoma (PDAC) treatment is severely limited by lack of effective KRAS suppression strategies. To address this dilemma, a reactive oxygen species (ROS)-responsive and PDAC-targeted nanodrug named Z/B-PLS was constructed to confront KRAS through dual-blockade of its downstream PI3K/AKT/mTOR and RAF/MEK/ERK for enhanced PDAC treatment. Specifically, photosensitizer zinc phthalocyanine (ZnPc) and PI3K/mTOR inhibitor BEZ235 (BEZ) were co-loaded into PLS which was constructed by click chemistry conjugating MEK inhibitor selumetinib (SEL) to low molecular weight heparin with ROS-responsive oxalate bond. The BEZ and SEL blocked PI3K/AKT/mTOR and RAF/MEK/ERK respectively to remodel glycolysis and non-canonical glutamine metabolism. ZnPc mediated photodynamic therapy (PDT) could enhance drug release through ROS generation, further facilitating KRAS downstream dual-blockade to create treatment-promoting drug delivery-therapeutic positive feedback. Benefiting from this broad metabolic modulation cascade, the metabolic symbiosis between normoxic and hypoxic tumor cells was also cut off simultaneously and effective tumor vascular normalization effects could be achieved. As a result, PDT was dramatically promoted through glycolysis-non-canonical glutamine dual-metabolism regulation, achieving complete elimination of tumors in vivo. Above all, this study achieved effective multidimensional metabolic modulation based on integrated smart nanodrug delivery, helping overcome the therapeutic challenges posed by KRAS mutations of PDAC.

Nonclinical evaluation of chronic cardiac contractility modulation on 3D human engineered cardiac tissues.

INTRODUCTION: Cardiac contractility modulation (CCM) is a medical device-based therapy delivering non-excitatory electrical stimulations to the heart to enhance cardiac function in heart failure (HF) patients. The lack of human in vitro tools to assess CCM hinders our understanding of CCM mechanisms of action. Here, we introduce a novel chronic (i.e., 2-day) in vitro CCM assay to evaluate the effects of CCM in a human 3D microphysiological system consisting of engineered cardiac tissues (ECTs). METHODS: Cryopreserved human induced pluripotent stem cell-derived cardiomyocytes were used to generate 3D ECTs. The ECTs were cultured, incorporating human primary ventricular cardiac fibroblasts and a fibrin-based gel. Electrical stimulation was applied using two separate pulse generators for the CCM group and control group. Contractile properties and intracellular calcium were measured, and a cardiac gene quantitative PCR screen was conducted. RESULTS: Chronic CCM increased contraction amplitude and duration, enhanced intracellular calcium transient amplitude, and altered gene expression related to HF (i.e., natriuretic peptide B, NPPB) and excitation-contraction coupling (i.e., sodium-calcium exchanger, SLC8). CONCLUSION: These data represent the first study of chronic CCM in a 3D ECT model, providing a nonclinical tool to assess the effects of cardiac electrophysiology medical device signals complementing in vivo animal studies. The methodology established a standardized 3D ECT-based in vitro testbed for chronic CCM, allowing evaluation of physiological and molecular effects on human cardiac tissues.

Comparative Analysis of Psychophysiological Responses in Fibromyalgia Patients: Evaluating Neuromodulation Alone, Neuromodulation Combined with Virtual Reality, and Exercise Interventions.

BACKGROUND AND OBJECTIVES: Fibromyalgia, a chronic condition, manifests as widespread musculoskeletal pain, fatigue, sleep disturbances, autonomic and cognitive dysfunction, hypersensitivity to stimuli, and various somatic and psychiatric symptoms. This study, a controlled and randomized experiment, aimed to evaluate and compare the immediate effects of different treatments on fibromyalgia patients. MATERIALS AND METHODS: The treatments included the EXOPULSE Mollii suit, a combination of the EXOPULSE Mollii suit with a virtual reality (VR) protocol, and a physical exercise regimen. A cohort of 89 female fibromyalgia patients was randomly assigned to one of four groups: Control (n = 20), Suit only (n = 22), Suit combined with VR (n = 21), and Exercise (n = 26). RESULTS: This study found notable differences across the groups in several key parameters. In the Control group, significant changes were observed in Forced Expiratory Volume (FEV 1/FEV 6), the Numeric Rating Scale (NRS) for pain, Pressure Pain Threshold (PPT) at the epicondyle, cortical arousal levels, the 10 m up-and-go test, and in all measured variables related to temperature and muscle oxygenation. For the group using the suit alone, there were significant differences noted in the NRS, the chair stand test, palm temperature, and all muscle oxygenation parameters. The Suit + VR group showed significant changes in the NRS, PPT at the knee, handgrip strength test, the 10 m up-and-go test, one-leg balance test with the right leg, muscle oxygen saturation (SmO2), deoxygenated hemoglobin (HHb), and oxygenated hemoglobin (O2Hb). Finally, the Exercise group exhibited significant differences in FEV 1/FEV 6, chest perimeter difference, NRS, PPT at both the epicondyle and knee, cortical arousal, the chair stand test, the 10-m up-and-go test, and in SmO2, HHb, and O2Hb levels. CONCLUSIONS: combining neuromodulation with VR and targeted exercise regimens can effectively alleviate fibromyalgia symptoms, offering promising avenues for non-pharmacological management.

The Physiological and Clinical-Behavioral Effects of Heart Rate Variability Biofeedback in Adolescents with Autism: A Pilot Randomized Controlled Trial.

Adolescents with autism present lower levels of cardiac vagal modulation. It was hypothesized that Heart Rate Variability Biofeedback (HRVB) increases cardiac vagal modulation in adolescents with autism, resulting in positive effects on physiological and psychosocial parameters. It was also hypothesized that home-based HRVB training is feasible. In a single-blind, randomized sham-controlled pilot trial, adolescents with autism performed supervised HRVB (n = 24) or sham training (n = 20). Subsequently, half of the adolescents received HRVB training at home, whereas the other subset did not practice. Physiological, cortisol and behavioral data were collected during stress-provoking assessments before and after each training period. Supervised HRVB resulted in a late increase in cardiac vagal modulation in adolescents with autism. Heart rate increased and cortisol decreased significantly immediately after supervised HRVB, but none of these effects remained after follow-up. Following supervised HRVB, no significant change in psychosocial functioning was found. Home-based HRVB was feasible, adolescents reported lower symptoms of stress, but a significant decrease in compliance rate was found. HRVB is feasible and effective in adolescents with autism given the late-emerging increases in cardiac vagal modulation and decrease in stress symptoms. Replicating this study with a larger sample and further exploration of the working mechanisms of HRVB are recommended. ClinicalTrials.gov , NCT04628715.

Vitamin D as a Modulator of Neuroinflammation: Implications for Brain Health.

Neuroinflammation represents a critical immune response within the brain, playing a pivotal role in defense against injury and infection. However, when this response becomes chronic, it can contribute to the development of various neurodegenerative and psychiatric disorders. This bibliographic review delves into the role of vitamin D in modulating neuroinflammation and its implications for brain health, particularly in the context of neurological and psychiatric disorders. While vitamin D is traditionally associated with calcium homeostasis and bone health, it also exerts immunomodulatory and neuroprotective effects within the central nervous system. Through comprehensive analysis of preclinical and clinical studies, we uncover how vitamin D, acting through its receptors in glial cells, may influence the production of proinflammatory cytokines and antioxidants, potentially mitigating the cascade of events leading to neuronal damage. Clinical research has identified vitamin D deficiency as a common thread in the increased risks of multiple sclerosis, Parkinson's disease, Alzheimer's, and depression, among others. Furthermore, preclinical models suggest vitamin D's regulatory capacity over inflammatory mediators, its protective role against neuronal apoptosis, and its contribution to neurogenesis and synaptic plasticity. These insights underscore the potential of vitamin D supplementation not only in slowing the progression of neurodegenerative diseases but also in improving the quality of life for patients suffering from psychiatric conditions. Future clinical studies are essential to validate these findings and further our understanding of vitamin D's capacity to prevent or alleviate symptoms, opening new avenues for therapeutic strategies against neuroinflammation-related pathologies. Neuroinflammation is a crucial immune response in the brain against injuries or infections, but its persistence can lead to diseases such as Alzheimer's, Parkinson's, multiple sclerosis, and depression. Cholecalciferol (Vitamin D3) emerges as a regulator of neuroinflammation, present in brain cells such as astrocytes and microglia, modulating immune function. Vitamin D's mechanisms of action include cytokine modulation and regulation of nuclear and mitochondrial genes. It adjusts inflammatory mediators and antioxidants, resulting in neuroprotective effects. Additionally, vitamin D impacts neurotransmitter synthesis and brain plasticity. This positions vitamin D as a potential adjunct in treating diseases like Alzheimer's and Parkinson's. Lastly, its role in intestinal microbiota and serotonin synthesis contributes to psychiatric disorders like schizophrenia and depression. Thus, vitamin D presents a novel therapeutic approach for neuroinflammatory, neurodegenerative, and neuropsychiatric diseases.

Effects of Traditional Chinese Medicine "Fuzheng Qingdu Decoction" on Autonomic Function and Cancer-Related Symptoms in Patients with Advanced Gastric Cancer undergoing Chemotherapy: A Controlled Trial.

OBJECTIVE: To evaluate the effects of Fuzheng Qingdu Decoction (FZQDD) on the autonomic function and cancer-related symptoms of patients with advanced gastric cancer undergoing chemotherapy to verify its clinical efficacy. METHODS: Sixty-two patients with stage III or IV gastric cancer were included in this study. The patients were divided into 2 groups: the chemotherapy (33 patients) and chemotherapy with FZQDD (29 patients) groups. The primary outcome was the autonomic function of the patients before and after the interventions. The parameters that were used to assess autonomic function were deceleration capacity (DC) and acceleration capacity (AC) of heart rate and heart rate variability (HRV), which comprised standard deviation of the normal-normal interval (SDNN), root mean square of successive interval differences (RMSSD), low-frequency power (LF), high-frequency power (HF), total power (TP), and LF-HF ratio. The secondary outcomes were cancer-related symptoms and the quality of life. RESULTS: DC and HRV parameters (ie, SDNN, RMSSD, LF, HF, and TP) were significantly decreased in the chemotherapy group; however, AC significantly increased after the interventions. No significant differences were observed in the DC, AC, and HRV parameters before and after the interventions in the chemotherapy with FZQDD group. Nevertheless, the changes in DC, AC, and HRV parameters (SDNN, RMSSD, HF, and TP) before and after the interventions were statistically significant between both the groups. FZQDD significantly improved the cancer-related symptoms and the quality of life of the patients. CONCLUSIONS: Oxaliplatin combined with S-1 (tegafur, gimeracil, and oteracil potassium) can impair autonomic modulation in patients with advanced gastric cancer. FZQDD can alleviate autonomic dysfunction by increasing the parasympathetic activity and decreasing the sympathetic tone, helping patients restore the dynamic sympathovagal balance, and significantly improving the cancer-related symptoms and the quality of life of patients.

α-lipoic acid modulates prostate cancer cell growth and bone cell differentiation.

Prostate cancer (PCa) progression leads to bone modulation in approximately 70% of affected men. A nutraceutical, namely, α-lipoic acid (α-LA), is known for its potent anti-cancer properties towards various cancers and has been implicated in treating and promoting bone health. Our study aimed to explore the molecular mechanism behind the role of α-LA as therapeutics in preventing PCa and its associated bone modulation. Notably, α-LA treatment significantly reduced the cell viability, migration, and invasion of PCa cell lines in a dose-dependent manner. In addition, α-LA supplementation dramatically increased reactive oxygen species (ROS) levels and HIF-1α expression, which started the downstream molecular cascade and activated JNK/caspase-3 signaling pathway. Flow cytometry data revealed the arrest of the cell cycle in the S-phase, which has led to apoptosis of PCa cells. Furthermore, the results of ALP (Alkaline phosphatase) and TRAP (tartrate-resistant acid phosphatase) staining signifies that α-LA supplementation diminished the PCa-mediated differentiation of osteoblasts and osteoclasts, respectively, in the MC3T3-E1 and bone marrow macrophages (BMMs) cells. In summary, α-LA supplementation enhanced cellular apoptosis via increased ROS levels, HIF-1α expression, and JNK/caspase-3 signaling pathway in advanced human PCa cell lines. Also, the treatment of α-LA improved bone health by reducing PCa-mediated bone cell modulation.

Dietary probiotic Lacticaseibacillus paracasei NSMJ56 modulates gut immunity and microbiota in laying hens.

This study was performed to investigate supplementary effects of probiotic Lacticaseibacillus paracasei NSMJ56 strain on laying performance, egg quality, intestinal histology, antioxidant status, gut immunity and microbiota in laying hens. A total of ninety-six 21-wk-old Hy-Line Brown laying hens were randomly subjected to one of 2 dietary treatments: a control group fed a non-supplemented diet, or a probiotic group fed with a diet supplemented with 1 g of Lacticaseibacillus paracasei NSMJ56 (5 × 108 CFU/kg of diet). The trial lasted for 4 wk. Egg weight was increased (P < 0.05) in laying hens fed probiotic-fed diet compared with the control group. Dietary probiotics did not affect egg quality except for Haugh unit, which was improved (P < 0.05) in the probiotic-fed group. Neither jejunal histology nor cecal short-chain fatty acids were affected by dietary treatments. Dietary probiotics increased the activity of catalase compared with the control group. Flow cytometry analysis revealed that dietary probiotics elevated the CD4+ T cells, but not CD8+ T cells, in jejunal lamina propria. Based on the LEfSe analysis at the phylum and genus levels, Erysipelotrichales, Erysipelotrichia, Flintibater, Dielma, Hespellia, Coprobacter, Roseburia, Anaerotignum, and Coprococcus were enriched in the probiotic group compared with the control group. Taken together, our study showed that dietary probiotics could be used to improve some parameters associated with egg freshness and antioxidant capacity, and to partially alter T cell population and microbial community in laying hens.

Unraveling the potential of vitamins C and D as adjuvants in depression treatment with escitalopram in an LPS animal model.

Depression is linked with oxidative stress and inflammation, where key players include nitric oxide (NO), nuclear factor erythroid 2-related factor 2 (Nrf2), Brain-Derived Neurotrophic Factor (BDNF), and Heme Oxidase-1 (HO-1). Augmenting the efficacy of antidepressants represents a compelling avenue of exploration. We explored the potential of vitamins C and D as adjuncts to escitalopram (Esc) in a lipopolysaccharide (LPS)-induced depression model focusing on the aforementioned biomarkers. Male Swiss albino mice were stratified into distinct groups: control, LPS, LPS + Esc, LPS + Esc + Vit C, LPS + Esc + Vit D, and LPS + Esc + Vit C + Vit D. After a 7-day treatment period, a single LPS dose (2 mg/kg), was administered, followed by comprehensive assessments of behavior and biochemical parameters. Notably, a statistically significant (p < 0.05) alleviation of depressive symptoms was discerned in the Esc + Vit C + Vit D group versus the LPS group, albeit with concomitant pronounced sedation evident in all LPS-treated groups (p < 0.05). Within the cortex, LPS reduced (p < 0.05) the expression levels of NOx, Nrf2, BDNF, and HO-1, with only HO-1 being reinstated to baseline in the LPS + Esc + Vit D and the LPS + Esc + Vit C + Vit D groups. Conversely, the hippocampal NOx, Nrf2, and HO-1 levels remained unaltered following LPS administration. Notably, the combination of Esc, Vit C, and Vit D effectively restored hippocampal BDNF levels, which had been diminished by Esc alone. In conclusion, vitamins C and D enhance the therapeutic effects of escitalopram through a mechanism independent of Nrf2. These findings underscore the imperative need for in-depth investigations.

Tumor microenvironment-activated theranostic nanozymes for trimodal imaging-guided combined therapy.

Synergistic therapy is expected to be a promising strategy for highly effective cancer treatment. However, the rational design of a simple and multifunctional nanoplatform still remains a grand challenge. Considering the nature of weak acidic, hypoxic, and H2O2 abundant tumor microenvironment, we constructed an indocyanine green (ICG) modified platinum nanoclusters (Pt NCs) decorated gold nanobipyramids (Au NBPs) to form the multifunctional nanocomposites (Au NBPs@Pt NCs-ICG) for multimodal imaging mediated phototherapy and chemodynamic cancer therapy. The photosensitizer ICG was covalently linked to Au NBPs@Pt NCs by bridging molecules of SH-PEG-NH2 for both photodynamic therapy (PDT) and fluorescence imaging. Besides, Au NBPs@Pt NCs-ICG nanocomposites exhibited catalase- and peroxidase-like activities to generate O2 and ·OH, which relieved the tumor hypoxia and upregulated antitumoral ROS level. Moreover, the combination of Au NBPs and ICG endowed the Au NBPs@Pt NCs-ICG with super photothermal conversion for effective photothermal imaging and therapy. In addition, the Au NBPs@Pt NCs-ICG nanoplatform displayed excellent X-ray computed tomography (CT) imaging ability due to the presence of high-Z elements (Au and Pt). Overall, our results demonstrated that Au NBPs@Pt NCs-ICG nanoplatform exhibited a multimodal imaging guided synergistic PTT/PDT/CDT therapeutic manners and held great potential as an efficient treatment for breast cancer.

Paving new roads toward the advancement of broad-spectrum antiviral agents.

Broad-spectrum antivirals (BSAs) have the advantageous property of being effective against a wide range of viruses with a single drug, offering a promising therapeutic solution for the largely unmet need in treating both existing and emerging viral infections. In this review, we summarize the current strategies for the development of novel BSAs, focusing on either targeting the commonalities during the replication of multiple viruses or the systemic immunity of humans. In comparison to BSAs that target viral replication, these immuno-modulatory agents possess an expanded spectrum of antiviral activity. However, antiviral immunity is a double-edged sword, and maintaining immune homeostasis ultimately dictates the health status of hosts during viral infections. Therefore, establishing an ideal goal for immuno-modulation in antiviral interventions is crucial. Herein we propose a bionic approach for immuno-modulation inspired by mimicking bats, which possess a more robust immune system for combating viral invasions, compared to humans. In addition, we discuss an empirical approach to treat diverse viral infections using traditional Chinese medicines (TCMs), mainly through bidirectional immuno-modulation to restore the disrupted homeostasis. Advancing our understanding of both the immune system of bats and the mechanisms underlying antiviral TCMs will significantly contribute to the future development of novel BSAs.

Investigation on Anti-diabetic Efficacy of a Cucurbitaceae Food Plant from the North-East Region of India: Exploring the Molecular Mechanism through Modulation of Oxidative Stress and Glycosylated Hemoglobin (HbA1c).

BACKGROUND: The medicinal plants of the Cucurbitaceae family, such as Solena heterophylla Lour. fruits, have significant ethnobotanical value and are readily accessible in North East India. AIMS: We conducted a study on Solena heterophylla Lour. fruits to evaluate their anti-diabetic activity in vivo, standardize their HPTLC, and profile their metabolites using LC-QTOF-MS. We aimed to explore the molecular mechanism behind their effects on oxidative stress and glycosylated hemoglobin (HbA1c). METHODS: Firstly, the ethyl acetate fraction of Solena heterophylla Lour. fruits was standardized using Cucurbitacin B as a standard marker by conducting HPTLC evaluation. Next, we delved into analyzing metabolite profiling. In addition, the standardized fraction was utilized in an experimental study to investigate the molecular mechanism of action in an in vivo high-fat diet and a low dose of streptozotocin-induced diabetic model. RESULTS: We have reportedly identified 52 metabolites in the ethyl acetate fraction of Solena heterophylla (EASH). In the in vitro tests, it has been observed that this extract from plants possesses notable inhibitory properties against α-amylase and α-glucosidase. Solena heterophylla fruits with high levels of Cucurbitacin B (2.29% w/w) helped lower FBG levels in animals with EASH treatment. EASH treatment reduced HbA1c levels and normalized liver lipid peroxidation and antioxidant enzyme levels. SGOT, SGPT, and SALP serum enzyme levels also returned to normal. CONCLUSION: Based on the current evaluation, it was found that EASH exhibited encouraging hypoglycemic effects in diabetic rats induced by a low dose of STZ and high-fat diet, which warrants further investigation.

Making Sense of Electrical Stimulation: A Meta-analysis for Wound Healing.

Electrical stimulation as a mode of external enhancement factor in wound healing has been explored widely. It has proven to have multidimensional effects in wound healing including antibacterial, galvanotaxis, growth factor secretion, proliferation, transdifferentiation, angiogenesis, etc. Despite such vast exploration, this modality has not yet been established as an accepted method for treatment. This article reviews and analyzes the approaches of using electrical stimulation to modulate wound healing and discusses the incoherence in approaches towards reporting the effect of stimulation on the healing process. The analysis starts by discussing various processes adapted in in vitro, in vivo, and clinical practices. Later it is focused on in vitro approaches directed to various stages of wound healing. Based on the analysis, a protocol is put forward for reporting in vitro works in such a way that the outcomes of the experiment are replicable and scalable in other setups. This work proposes a ground of unification for all the in vitro approaches in a more sensible manner, which can be further explored for translating in vitro approaches to complex tissue stimulation to establish electrical stimulation as a controlled clinical method for modulating wound healing.

An overview of systematic reviews examining the quantitative sensory testing-derived hypoalgesic effects of manual therapy for musculoskeletal pain.

BACKGROUND: Changes in quantitative sensory testing (QST) after manual therapy can provide insight into pain relief mechanisms. Prior systematic reviews have evaluated manual-therapy-induced QST change. This overview of systematic reviews aims to consolidate this body of literature and critically review evidence on the hypoalgesic effects of manual therapy in clinical populations. METHODS: A comprehensive search was conducted on PubMed, CINAHL, PsycInfo, and Embase. Peer-reviewed systematic reviews with or without meta-analysis were eligible if the reviews examined the effect of manual therapy compared to non-manual therapy interventions on QST outcomes in clinical populations. Methodological quality was assessed with the AMSTAR 2 tool. Meta-analysis results and qualitative (non-meta-analysis) interpretations were summarized by type of manual therapy. Overlap of studies was examined with the corrected covered area (CCA) index. RESULTS: Thirty systematic reviews, including 11 meta-analyses, met inclusion. There was a slight overlap in studies (CCA of 1.72% for all reviews and 1.69% for meta-analyses). Methodological quality was predominantly low to critically low. Eight (27%) reviews examined studies with a range of manual therapy types, 13 (43%) reviews focused on joint-biased manual therapy, 7 (23%) reviews focused on muscle-biased manual therapy, and 2 (7%) reviews focused on nerve-biased manual therapy. Twenty-nine (97%) reviews reported on pressure pain threshold (PPT). Meta-analytic results demonstrated conflicting evidence that manual therapy results in greater hypoalgesic effects compared to other interventions or controls. CONCLUSION: Our overview of QST effects, which has relevance to mechanisms underlying hypoalgesia, shows conflicting evidence from mostly low to critically low systematic reviews.

Response to tibial and sacral nerve modulation in overactive bladder: Is there any correlation?

OBJECTIVES: To assess the correlation between the response to transcutaneous tibial nerve stimulation (TTNS) and subsequent response to sacral nerve modulation (SNM) to treat overactive bladder (OAB). MATERIALS AND METHODS: All patients who consecutively received TTNS followed by a two-stage SNM between January 2016 and June 2022 to treat OAB in two university hospital centers were included. The response to each therapy was evaluated with success defined by a 50% or greater improvement in one or more bothersome urinary symptoms from baseline. The primary endpoint was the statistical relationship between the response to TTNS and the response to SNM, assessed by logistic regression. Secondary endpoints were the statistical relationship between the response to TTNS and the response to SNM when controlling for gender, age (<57 years vs. >57 years), presence of an underlying neurological disease, and presence of DO, adding the factor and interaction to the previous regression model. RESULTS: Among the 92 patients enrolled in the study, 68 of them were women (73.9%), and the median age was 57.0 [41.0-69.0] years. The success was reported in 22 patients (23.9%) under TTNS and 66 patients (71.7%) during the SNM test phase. There was no statistical correlation between response to TTNS and response to SNM in the overall population (confidence interval: 95% [0.48-4.47], p = 0.51). Similarly, there was no statistical correlation when controlling for age <57 years or ≥57 years, with p = 1.0 and p = 0.69, respectively. No statistical study could be conducted for the other subpopulations due to small sample sizes. CONCLUSION: The response to TTNS does not predict the response to SNM in the treatment of OAB. TTNS and SNM should be considered as separate therapies, and the decision-making process for OAB treatment should take this into account.

Chemical Profile and Biological Activities Of Piper mikanianum (Kunth) Steud Essential Oil for Development and Improvement of Oral Rinse.

INTRODUCTION: Studies prove that the use of medicinal plants is a custom carried out by man since ancient times, the evolution of the pharmaceutical industry makes more people consume more natural products. Currently, we can observe that mouthwashes containing natural compounds have shown a growth in demand in the markets and in the professional community. OBJECTIVE: The present study aims to carry out the chemical characterization and microbiological potential of Piper mikanianum (Kunth) Steud essential oil (EOPm), providing data that allows the development of a low-cost mouthwash formulation aimed at vulnerable communities. METHODS: The evaluation of the antibacterial activity and modulator of bacterial resistance was performed by the microdilution method to determine the minimum inhibitory concentration (MIC). The chemical components were characterized by gas chromatography coupled to mass spectrometry, identified 28 constituents, in which Safrole Phenylpropanoid is the major compound, representing 72.6 % of the total composition, followed by α-pinene (10.7 %), Limonene (2 %), ß-caryophyllene (2 %), E-nerolidol (1.9 %), spathulenol (1.3 %) and camphene (1.1 %). RESULTS: The EOPm showed a MIC minimum inhibitory concentration≥1024 µg/mL for all bacterial strains used in the tests. When the EOPm modulating activity combined with chlorhexidine, mouthwash, ampicillin, gentamicin and penicillin G was evaluated against bacterial resistance, the oil showed significant synergistic activity, reducing the MIC of the products tested in combination, in percentage between 20.6 % to 98 .4 %. CONCLUSIONS: We recommend the expansion of tests with greater variation of EOPm concentration combinations and the products used in this study, as well as toxicity evaluation and in vivo tests, seeking the development of a possible low-cost mouthwash formulation accessible to the most vulnerable population.

Anti-Acidification and Immune Regulation by Nano-Ceria-Loaded Mg-Al Layered Double Hydroxide for Rheumatoid Arthritis Therapy.

Rheumatoid arthritis (RA) is a chronic autoimmune disease featuring an abnormal immune microenvironment and resultant accumulation of hydrogen ions (H+ ) produced by activated osteoclasts (OCs). Currently, clinic RA therapy can hardly achieve sustained or efficient therapeutic outcomes due to the failures in generating sufficient immune modulation and manipulating the accumulation of H+ that deteriorates bone damage. Herein, a highly effective immune modulatory nanocatalytic platform, nanoceria-loaded magnesium aluminum layered double hydroxide (LDH-CeO2 ), is proposed for enhanced immune modulation based on acid neutralization and metal ion inherent bioactivity. Specifically, the mild alkaline LDH initiates significant M2 repolarization of macrophages triggered by the elevated antioxidation effect of CeO2 via neutralizing excessive H+ in RA microenvironment, thus resulting in the efficient recruitment of regulatory T cell (Treg) and suppressions on T helper 17 cell (Th 17) and plasma cells. Moreover, the osteogenic activity is stimulated by the Mg ion released from LDH, thereby promoting the damaged bone healing. The encouraging therapeutic outcomes in adjuvant-induced RA model mice demonstrate the high feasibility of such a therapeutic concept, which provides a novel and efficient RA therapeutic modality by the immune modulatory and bone-repairing effects of inorganic nanocatalytic material.

Immunomodulatory effect of vitamin D supplementation on Behçet's disease patients: effect on nitric oxide and Th17/Treg cytokines production.

INTRODUCTION: In the last decade, an immuno-modulatory effect of vitamin D supplementation have emerged as a potential therapeutic approach for some inflammatory and autoimmune diseases. As previously reported, vitamin D deficiency was strongly linked to several diseases as Behçet's disease (BD). BD is a chronic systemic inflammatory disorder with autoimmunity, genetic and environmental factors involvement. The aim of our current study is to set up a new therapeutic strategy in BD, combining conventional therapy and vitamin D supplementation. MATERIALS AND METHODS: Blood samples were collected from active and inactive BD patients and healthy controls (HC) to evaluate 25(OH) vitamin D levels using an electrochemiluminescence method. All deficient and insufficient vitamin D BD patients' were supplemented with vitamin D3 (CHOLECALCIFEROL, 200 000 UI/1 ml). In this context, NO, IL-17A and IL-10 levels were evaluated in patients and HC in vivo and ex vivo using Griess and ELISA methods respectively. RESULTS: Before supplementation, we noted with interest that BD patients had vitamin D deficiency, associated with elevated in vivo and ex vivo NO and IL-17A levels compared to HC. Conversely, low IL-10 levels were observed in the same BD patients in comparison to HC. Interestingly, restored vitamin D status in supplemented BD patients was related to the decreased NO levels. In the same way, the IL-10/IL-17A ratio was improved. CONCLUSIONS: Collectively, our data suggest that vitamin D supplementation in combination with conventional treatments has a beneficial effect and could constitute a good therapeutic candidate for alleviating inflammatory responses during Behçet disease.