Therapeutic Action Research Articles

Pharmacological mechanisms of carvacrol against hepatocellular carcinoma by network pharmacology and molecular docking

Background Preclinical studies have demonstrated that carvacrol possesses various biological and pharmacological properties, including anti-hepatocellular carcinoma (HCC) effects. However, the molecular basis of its therapeutic action on HCC remains unclear. Objective The aim of this study was to investigate and further validate the multi-target therapeutic mechanism of carvacrol against HCC. Methods The chemical structure of carvacrol was obtained from the PubChem database, and its potential targets were identified using SwissTargetPrediction, HERB, and BATMAN-TCM. HCC-specific genes were screened from the TCGA-LIHC cohort. The therapeutic targets of carvacrol against HCC were determined through the intersection of these datasets. Subsequently, a multivariate Cox regression prognostic model was established. Molecular docking was performed to analyze the interactions between carvacrol and its therapeutic targets. Additionally, molecular dynamics simulations were conducted to validate the molecular docking results using Discovery Studio 2019 software. Results A total of 223 carvacrol targets and 882 HCC-specific genes were identified. Fifteen therapeutic targets of carvacrol against HCC were obtained, including CA2, AR, ALB, AURKA, ALPL, EPHX2, BCHE, IL1RN, AGRN, CRP, DMGDH, APOA1, SOX9, HPX, and CHKA. The prognostic model accurately and independently predicted survival outcomes. AGRN and AURKA were significantly associated with HCC overall survival. Molecular docking and molecular dynamics simulations demonstrated that carvacrol exhibited strong potential for stable binding to the therapeutic targets AGRN and AURKA. Conclusion Our findings elucidate the multi-target mechanism of action of carvacrol against HCC, providing a foundation for future research on its application in HCC management.

Thermo-Responsive Polymer-Based Nanoparticles: From Chemical Design to Advanced Applications.

Thermo-responsive polymers have emerged as a cutting-edge tool in nanomedicine, paving the way for innovative approaches to targeted drug delivery and advanced therapeutic strategies. These "smart" polymers respond to temperature changes, enabling controlled drug release in pathological environments characterized by high temperatures. By exploiting their unique phase transition, occurring at the lower or upper critical solution temperatures (LCST and UCST), these systems ensure localized therapeutic action, minimizing collateral damage to healthy tissues. The integration of these polymers into nanoparticles with hydrophilic shells and hydrophobic cores enhances their stability and biocompatibility. Furthermore, advanced polymer engineering allows precise modulation of LCST and UCST through adjustments in composition and hydrophilic-lipophilic balance, optimizing their responsiveness for specific applications. In addition to drug delivery, thermo-responsive nanoparticles are gaining attention in several fields such as gene therapy and imaging. Therefore, this review explores the chemical and structural diversity of thermo-responsive nanoparticles, emphasizing their ability to encapsulate and release drugs effectively. Second, this review highlights the potential of thermo-responsive nanoparticles to redefine treatment paradigms, providing a comprehensive understanding of their mechanisms, applications, and future perspectives in biomedical research.

Mechanism of Traditional Chinese Medicine extract in the treatment of diabetic erectile dysfunction.

Diabetic erectile dysfunction (DED) is a prevalent but often overlooked microvascular complication of type 2 diabetes mellitus (T2DM), with strong associations to cardiovascular disease. The pathophysiology of erectile dysfunction (ED) in T2DM patients is more intricate than in non-diabetic individuals, likely involving multiple pathogenic mechanisms such as endothelial dysfunction, vascular alterations, neuropathy, and oxidative stress. Traditional Chinese Medicine (TCM) has long been utilized in the management of DED, drawing on an extensive body of clinical experience. In TCM, DED is typically attributed to imbalances such as renal yang deficiency or insufficiencies in qi and blood. Herbal therapies within the TCM framework offer a multifaceted approach to treatment, targeting not only the replenishment of kidney yang and the regulation of qi and blood but also incorporating strategies for glycemic control and renal protection. This holistic approach has demonstrated effectiveness in alleviating erectile dysfunction in diabetic patients, thereby improving quality of life. However, the complexity of Chinese herbal formulations, with their diverse bioactive constituents, complicates the identification of specific active compounds and the mechanistic understanding of their therapeutic actions. This complexity has contributed to ongoing skepticism regarding the clinical utility of TCM and herbal remedies in the treatment of DED. This study aimed to investigate the pathological mechanisms underlying the therapeutic effects of TCM in the treatment of DED, with a specific focus on the associated signaling pathways. By elucidating these mechanisms, the study seeks to provide a scientific basis for novel therapeutic strategies and enhance the viability of TCM-based approaches for DED management. Future research should prioritize the development of efficacious Chinese patent medicines tailored for the treatment of DED. This study utilizes keywords such as "diabetic erectile dysfunction", "signaling pathways", "traditional Chinese Medicine", "bioactive compounds", "herbal", "herbal monomers", and "herbal extracts" to conduct a comprehensive literature search in databases including Embase, PubMed, Web of Science, CNKI, Wanfang, and VIP, spanning all relevant publications up to February 2024. It has been demonstrated that TCM extract can treat the DED by influencing the signaling pathways involved. A comprehensive literature review was conducted across multiple databases, followed by rigorous screening, exclusion, summarization, synthesis, and analysis of relevant studies. The results indicate that TCM for DED primarily targets key pathological features, including endothelial dysfunction, vascular and neural abnormalities, and oxidative stress. The underlying mechanisms involve the NO/cGMP, eNOS, and PI3K/Akt/mTOR signaling pathways, contributing to significant improvements in erectile function. These findings provide a scientific basis for the use of TCM in DED, offering viable therapeutic options and innovative strategies to advance TCM-based treatment approaches. Furthermore, TCM exhibits notable potential in mitigating the pathological progression of DED. The pharmacological mechanisms and molecular signaling pathways of TCM extracts have been extensively investigated, underscoring their high value for clinical research and therapeutic development.

Smart biomaterial gels for periodontal therapy: A novel approach.

Periodontitis, a chronic inflammatory condition of the oral cavity, is characterized by the progressive destruction of the supporting structures of the teeth. The pathogenic effects of periodontopathogens extend beyond the local periodontal environment, contributing to systemic health complications, thereby underscoring the need for effective therapeutic strategies. Current standard treatments, which involve mechanical debridement coupled with systemic anti-inflammatory and antibiotic therapies, are often associated with limited efficacy, adverse effects, and the emergence of antibiotic resistance. Recent advancements in localized drug delivery systems present an innovative alternative, offering site-specific targeting with sustained therapeutic action. Smart drug delivery platforms, designed to respond to the unique microenvironment of periodontal pockets, undergo physicochemical transformations such as gelation or controlled drug release, enhancing treatment efficacy. This review comprehensively explores the etiological and prognostic factors of periodontitis, critical diagnostic biomarkers, and an in-depth analysis of stimuli-responsive biomacromolecule-based gels. These systems are evaluated for their structural properties, biological compatibility, and therapeutic potential while addressing their limitations and barriers to clinical translation. By integrating insights into the interplay between material properties and biological performance, this review highlights the future role of these advanced delivery systems in overcoming challenges in periodontal healthcare. Such approaches aim to bridge the gap between bench-side innovation and bedside application, offering the transformative potential to enhance therapeutic outcomes and improve patient quality of life in managing periodontal diseases.

Memory-Enhancing and Anxiolytic Effects of the Rose of Jericho on Sleep Deprivation-Related Cognitive and Behavioral Changes.

Sleep is a crucial physiological phenomenon that enables the body to engage in restoration and rejuvenation. Remarkably, even limited periods of sleep deprivation (SD) can adversely affect cognitive functions such as memory retention, emotional regulation, data processing, and concentration. The Rose of Jericho (RoJ) has been considered more than a plant and has demonstrated potential therapeutic actions in childbirth, respiratory diseases, gastrointestinal disorders, and cancer.The effect of the RoJ on memory, cognition, and behavior has not yet been well-studied. The present study aimed to investigate the possible therapeutic effects of the RoJ on memory, cognition, behavior, and motor coordination in a rat model of SD. Thirty male Wistar albino rats weighing 120-150 g were used in the present study. The rats were acclimatized and trained and then randomly divided into three groups: control (C), sleep-deprived (SD), and SD treated with RoJ (SD+RoJ). Spatial memory and learning were assessed using the Morris Water Maze (MWM) test, while anxiety-related behaviors were evaluated through the Elevated Plus Maze (EPM) test. The rotarod test was used to assess motor coordination. The study revealed significant behavioral and cognitive performance improvements with the SD+RoJ group across all the tests. In the MWM test, the SD group exhibited a marked increase in test duration (29.5 ± 3.57 sec) and a reduction in average speed (1.9 ± 0.3 cm/s) when compared to the C group (13.41 ± 1.57 sec and 5.9 ± 0.34 cm/s, respectively). Interestingly, the SD+RoJ group significantly reduced test duration (19.75 ± 3.36 sec) and improved rats' speed (6.06 ± 0.27 cm/s) compared to the SD group. The EPM test demonstrated that the SD group spent significantly less time in the open arms (16.2 ± 9.44 sec) than the C group (59.8 ± 3.29 sec). Interestingly, the SD+RoJ group significantly improved the time spent in the open arms (45.8 ± 11.64 sec). Moreover, the SD+RoJ group showed notable improvement in open-arm entries (7 ± 2.39) compared to the SD group (1.6 ± 0.81). In the Rotarod test, the SD group demonstrated a significant decline in latency to fall (44.2 ± 9.5 sec) compared to the C group (228.67 ± 35.44 sec). The SD+RoJ group exhibited a significantly longer falling latency (165 ± 28.77 sec) than the SD group. Treatment with the RoJ alleviated SD-dependent cognitive impairment, anxiety, and decline in motor coordination. Supplementation with the RoJ may offer potential therapeutic benefits, including boosting memory, improving cognition, reducing anxiety and depression, andenhancing motor coordination.

Chromatographic Analysis of Polyherbal Extract and Formulation by HPTLC and GC-MS Methods

Background: The World Health Organization (WHO) acknowledges that natural plants and their bioactive components have been recognized for their potential therapeutic benefits. The main issue facing the herbal industry is the lack of effective quality control for herbal extracts and formulations Establishment standards are essential to ensuring the efficacy and integrity of natural medicine development. Determining the precise compound responsible for therapeutic action poses an equally challenging task, as these compounds frequently work synergistically to produce medicinal benefits. Aim: In this exploration, GC-MS and high-performance thin-layer chromatography were used to analyze the formulation and polyherb extract. The HPTLC technique is often employed to analyze the sample and compare its fingerprint to reference standards to verify plant extracts’ quality and formulations’ quality. Using GC-MS, the phytochemical ingredients in the formulation and the extract have been determined. Methods: This research assessed a mixture of herb extract and formulation using analytical approaches. The combined hydroalcoholic extracts of the herbs were used to produce the polyherb extract of seeds of Azadirachta indica, Carica papaya, Trigonella foenum-graecum, Gossipium herbaceum, fruit of Piper nigrum. The required excipients were added before compressing the herbal mixture extract into tablets. Results: The extract and formulation’s HPTLC chromatograms displayed Rf values of 0.14, 0.34, 0.48, 0.63, and 0.76.The results of the GC-MS, N-Hexadecanoic, 1,19-Eicosadiene, 9,12-Octadecadienoic Acid, Z, Z-4,16-Octadecadien-1-Ol Acetate, Piperine that were analyzed provide different peaks to determining the presence of phytochemicals found in the extract and formulation were confirmed. Conclusion: HPTLC and GC-MS aid in the identification of individual chemical constituents within herbal formulations by coupling chromatographic and mass spectral data of the sample with reference standards or databases, the identity of key compounds can be confirmed, ensuring authenticity, and has shown an intense correlation between the mixture of herb extract and formulation. Major Findings: In this Research, GC-MS and high-performance thin-layer chromatography were used to analyze the formulation and polyherbal extract of key compounds can be confirmed, ensuring authenticity, and has shown an intense correlation between the mixture of herb extract and formulation.

Use of endolaser associated with fractional CO2 laser for facial rejuvenation: Clinical experience in Brazil

Background: The Endolaser used in aesthetic procedures in Brazil is characterized by the use of equipment that emits wavelengths of 1470 nm and 980 nm. Its main therapeutic action is to generate intense heat in the subcutaneous tissues to damage adipose tissue and heat the skin to stimulate collagen production. The CO2 laser is recommended for different dermatological and aesthetic conditions and is a great resource for skin rejuvenation. The association of these two resources is viable due to their therapeutic actions on the skin. Objective: Considering that the Endolaser is already associated with several therapeutic resources, including fractional lasers, this study aimed to describe the clinical experience of the authors in Brazil regarding its use associated with the fractional CO2 laser for the treatment of facial aging. Material and Methods: This study is characterized by exploratory research presented through a narrative review, to describe the action of the Endolaser associated with the fractional CO2 laser in the treatment of facial aging. In addition to the literature review, some clinical findings obtained through a retrospective analysis of medical records were added to describe the authors' clinical experience in Brazil of using Endolaser associated with fractional CO2 laser in the treatment of facial aging. Results: The association of the Endolaser with the fractional CO2 laser proved to be effective and safe under the conditions described in this work. The Endolaser is the first resource to be applied, followed immediately by the fractional CO2 laser. After using the lasers, drug delivery is carried out with a cosmeceutical solution, and in order to accelerate the product’s drying on the skin, we cooled the skin with a jet of cold air. Then, with the skin dry, we sealed the treated region by applying 10% retinoic acid. The treatment is completed at home with the application of dexamethasone acetate, moisturizing cream and sunscreen. Conclusion: The combined treatment of Endolaser and fractional CO2 Laser proved to be efficient and safe, as long as the parameters and protocols suggested in this study are followed. Mainly respecting dermal tolerance to skin heating in order to enhance the results, as with this laser equipment we can optimize performance in different layers, as we understood that they are complementary therapies.

ASUHAN KEPERAWATAN PADA Tn.M SKIZOFRENIA HALUSINASI PENDENGARAN DENGAN INTERVENSI MENGONTROL HALUSINASI BERCAKAP-CAKAP DENGAN ORANG LAIN DI RUMAH SAKIT DR. RM SOEDJARWADI KLATEN

In Indonesia, the prevalence of schizophrenia/psychosis is around 6.7 per 1000 households. Hallucinations are a condition that befalls individuals with mental disorders which results in changes in the patient's subjective perception, which is characterized by the patient experiencing sensations such as sound, sight, taste and touch without any clear stimulation. If not treated immediately, the symptoms will get worse and can cause harm. self. One effective method for controlling schizophrenia is to encourage people to interact or converse with other people. The benefit of the activity is that it prevents hallucinations from occurring. The aim of the research is to determine the description of nursing care for patients with schizophrenic auditory hallucinations with a focus on the act of conversing with other people. Using descriptive methods by managing patients arranged in nursing care, functions to create systematic, real and precise descriptions of the facts. The results of focused therapeutic actions on conversing with other people for 3 days can reduce the signs and symptoms of auditory hallucinations. This is proven when conversing with other people, the patient focuses on the conversation and can avoid whispers that are not real to the patient. It was concluded that the technique of conversing with other people can prevent signs and symptoms of auditory hallucinations.

Therapeutic Actions of Hepatocyte Extracellular Vesicles in a Murine Model of Diet-Induced Steatohepatitis with Fibrosis

Therapeutic Actions of Hepatocyte Extracellular Vesicles in a Murine Model of Diet-Induced Steatohepatitis with Fibrosis

P0084 Secreted inflammatory protein profiles of human inflammatory bowel disease explants following treatment ex-vivo with licenced biologic therapies and patients’ in-vivo response

Abstract Background Patient-derived inflammatory bowel disease (IBD) ex-plants have potential for biomarker and therapy discovery. Infliximab (IFX), ustekinumab (UST) and vedolizumab (VDZ) are biologic therapies licenced for the induction and maintenance of remission in ulcerative colitis (UC) and Crohn’s disease (CD). All have demonstrated efficacy in IBD despite differing mechanisms of action. IBD explants have the potential to be used as a precision medicine tool, to gain further insights into disease biology and therapeutic mechanisms of action. We aimed to evaluate the effect of IFX, UST and VDZ on inflammatory protein secretion profiles in ex-vivo human IBD ex-plants, whilst comparing these explant secretome variations with in-vivo patient data of patients who commenced these therapies in clinic. Methods Patients with IBD due to commence in-vivo biologic therapy, undergoing endoscopy, were prospectively recruited. Endoscopic biopsies were collected from the sigmoid colon and IBD ex-plants generated as per previously described methods. IBD explants were then cultured for 24 hours with an IgG control vehicle, IFX, UST and VDZ. After 24 hours, tissue conditioned media (TCM) from IBD explants was collected. TCM secreted inflammatory protein profiles were quantified using 54 V-plex ELISA (Meso Scale Diagnostics, USA). Secreted inflammatory protein profiles were compared between IgG vehicle (control) and UST, IFX, VDZ treated ex-plants. Principal component analysis (PCA) was carried out to characterise the influence of biologics on ex-vivo explant secreted inflammatory profiles. Clinical responses of patients treated with biologics in-vivo were also compared with explants inflammatory profiles. Results 37 patients with were included (51% CD, 49% UC); age (median, [IQR]) 41[33-53] years, 49% male; disease duration (median, [IQR]) 9 [5-14] years. 23 patients were subsequently commenced on either IFX, UST or VDZ in-vivo and followed over 2 years to determine therapy response. PCA identified significant variation in the CD and UC secretome. Biologic therapy ex-vivo resulted in significant alterations and clustering in the UC secretome compared to control. Conclusion The IBD explant model recapitulates expected IBD pathology. These data demonstrate that significant differences between the CD and UC secretome. Treatment with licenced biologic therapies ex-vivo significantly alters multiple pro-inflammatory cytokines, chemokines and secreted proteins in IBD explants. Further study is required to completely understand the effects of licenced biologic therapies on the IBD tissue microenvironment.

Tubulin detyrosination shapes Leishmania cytoskeletal architecture and virulence

Tubulin detyrosination has been implicated in various human disorders and is important for regulating microtubule dynamics. While in most organisms this modification is restricted to α-tubulin, in trypanosomatid parasites, it occurs on both α- and β-tubulin. Here, we show that in Leishmania, a single vasohibin (LmVASH) enzyme is responsible for differential kinetics of α- and β-tubulin detyrosination. LmVASH knockout parasites, which are completely devoid of detyrosination, show decreased levels of glutamylation and exhibit a strongly diminished pathogenicity in mice, correlating with decreased proliferation in macrophages. Reduced virulence is associated with altered morphogenesis and flagellum remodeling in detyrosination-deficient amastigotes. Flagellum shortening in the absence of detyrosination is caused by hyperactivity of a microtubule-depolymerizing Kinesin-13 homolog, demonstrating its function as a key reader of the trypanosomatid-tubulin code. Taken together, our work establishes the importance of tubulin detyrosination in remodeling the microtubule-based cytoskeleton required for efficient proliferation in the mammalian host. This highlights tubulin detyrosination as a potential target for therapeutic action against leishmaniasis.

An Anticancer Bioactive Peptide Combined with Oxaliplatin Inhibited Gastric Cancer Cells In Vitro and In Vivo.

Gastric cancer has become one of the major diseases threatening human health. This study aimed to investigate the mechanism of an anticancer bioactive peptide (ACBP) combined with oxaliplatin (OXA) on MKN-45, SGC7901, and NCI-N87 differentiated human gastric cancer cells and GES-1 immortalized human gastric mucosal epithelial cells. The therapeutic effect and action mechanism of short-term intermittent ACBP combined with OXA on nude mice with human gastric cancer were also investigated. The half-maximal inhibitory concentrations of these agents in these cells were measured by an MTT assay, and cell morphological changes were observed by H&E staining. The expression of Lin28, miR-107, miR-609, and Let-7 in these four cell lines was determined by q-PCR after drug treatment. Lin28 protein expression in these four cell lines treated with these drugs was measured by western blotting. Furthermore, activity and quality of life were observed daily in all tumor-bearing nude mice, and the expression of Lin28 in tumor tissue was determined by immunohistochemistry and RT-PCR. The results showed that ACBP inhibited the proliferation of MKN-45, SGC7901, and NCI-N87 gastric cancer cells in a dose-dependent manner and weakly suppressed the proliferation of GES-1 cells. Moreover, its inhibitory effect on proliferation was stronger in poorly differentiated gastric cancer cells. ACBP, OXA, and the combination upregulated Lin28 gene expression in MKN-45 cells and downregulated it in SGC7901 and GES-1 cells. ACBP and the combination therapy downregulated Let-7 expression in MKN-45 cells and upregulated Let-7 expression in SGC7901 cells. The combination of ACBP with OXA demonstrated significant anticancer sensitization. Moreover, it also significantly improved the quality of life of tumor-bearing nude mice and reduced the toxic side effects of chemotherapeutic drugs on nude mice. ACBP alone and in combination with oxaliplatin influenced the expression of tumor stem cell marker gene Lin28 and regulated the expression of microRNAs specifically regulated by Lin28. In addition, the anticancer effects and attenuated sensitization effects of ACBP may be related to the Lin28/miRNA-107 signaling pathway, acting by inhibiting the proliferation of cancerous stem cells. The findings of this study provide a scientific basis for exploring the antitumor mechanism of ACBP alone and combined with chemotherapeutic drugs.

Targeting immune cellular populations and transcription factors: unraveling the therapeutic potential of JQF for NAFLD.

Non-alcoholic fatty liver disease (NAFLD) constitutes the most prevalent chronic liver disease worldwide. Progression to non-alcoholic steatohepatitis (NASH), the immune cell reservoir within the liver undergoes remodeling, exacerbating liver inflammation and potentially leading to liver fibrosis. Jiangtang Qingre Formula (JQF) is an effective prescription for the clinical treatment of NAFLD. However, its underlying mechanism of action remains unclear. Using a high-fat diet-induced NAFLD mouse model, we evaluated JQF's effects with biochemical tests and histopathology. Single-cell RNA sequencing and spatial transcriptomics furthered our understanding of NAFLD pathophysiology and JQF's treatment mechanisms. Our findings initially revealed significant improvements in JQF on hepatic steatosis, inflammation, fibrosis and glucose tolerance in NAFLD mice. Furthermore, significant changes were observed in the immune cells including monocytes, macrophages, and T cells in the livers of NAFLD mice. Notably, regions infiltrated by T cells presented the most severe liver inflammation and fibrosis. Importantly, JQF effectively modulated these immune cells. Advanced subcluster and cell communication analyses identified key macrophage (KCs, MoMFs) and T cell (Tc, Th2) subpopulations in JQF's therapeutic actions. Further SCENIC analysis additionally uncovered the essential transcription factors that regulate these cell subclusters, such as Stat2, Mta3, Eomes, and Etv5. Overall, our research suggests a promising potential therapeutic agent and identifies critical cell populations and transcription factors that contribute to its therapeutic effects, thereby revealing potential therapeutic targets for NAFLD.

Mesenchymal stromal cell-derived extracellular vesicles as nanotherapeutics for concanavalin a-induced hepatitis: modulating the gut‒liver axis

BackgroundAs cell-free nanotherapeutics, extracellular vesicles derived from mesenchymal stem cells (MSC-EVs) have shown potential therapeutic action against liver diseases. However, their effects on autoimmune hepatitis (AIH) are not yet well understood.Methods and resultsIn this study, we utilized a well-established concanavalin A (Con A)-induced fulminant hepatitis mouse model to investigate the effects of MSC-EVs on AIH. We found that MSC-EVs provide significant protection against Con A-induced hepatitis in C57BL/6 male mice, with their effectiveness being critically dependent on the gut microbiota. MSC-EVs modulate the composition of the gut microbiota, particularly by increasing the abundance of norank_f__Muribaculaceae, and impact liver metabolic profiles, leading to significant amelioration of liver injury. The identification of Acetyl-DL-Valine as a protective metabolite underscores the therapeutic potential of targeting gut‒liver axis interactions in liver diseases.ConclusionOverall, our data demonstrate that MSC-EVs exhibit nanotherapeutic potential in Con A-induced hepatitis and provide new insights into the treatment of autoimmune hepatitis.Graphical

Wolfberry (Lycium barbarum) glycopeptide attenuates dopaminergic neurons loss by inhibiting lipid peroxidation in Parkinson's disease

BackgroundParkinson's disease (PD) is a common neurodegenerative disorder characterized clinically by motor dysfunction due to gradual loss of dopaminergic neurons in the nigrostriatal system. Currently, medications such as levodopa preparations, offer only temporary symptomatic relief without preventing neuronal loss or halting disease progression. In traditional Chinese medicine (TCM), a particular type of wolfberry or goji berry, the fruit of Lycium barbarum L., has been historically regarded for its neuroprotective properties, potentially offering therapeutic benefits for PD. However, scientific validation of these effects remains limited. PurposeThis study aims to investigate the neuroprotective effects of wolfberry glycopeptide (WGP) on PD progression in various animal models, and to elucidate the underlying mechanisms responsible for its therapeutic action. Study designDiverse canonical animal models, including 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice, 6-hydroxydopamine (6-OHDA)-treated rats, and α-synuclein overexpressed hSNCAA53T mice, were used to evaluate WGP's anti-PD efficacy. Behavioral deficits and pathological damage to dopaminergic neurons were assessed to determine WGP's neuroprotective potential. MethodsAfter establishing the animal models and administering WGP treatment, PD-like behaviors were assessed using pole test, rotarod test and gait analysis. Dopaminergic neurons loss in the midbrain and striatum was detected by means of immunohistochemistry, immunofluorescence and Western blot analysis. Inflammatory markers in these brain regions were measured by ELISA. ResultsWGP treatment significantly alleviated motor deficits as well as progressive dopaminergic neurons loss. Mechanistically, WGP exerted its neuroprotective effects by regulating iron homeostasis, specifically through the modulation of key proteins such as TFRC, FTH1, and FPN. This function contributes to reducing the accumulation of lipid peroxidation in nigrostriatal system, thereby mitigating neuroinflammation and neuronal degeneration. ConclusionOur findings underscore the innovative potential of WGP as a neuroprotective agent in PD, with a unique mechanism of action targeting iron homeostasis and lipid peroxidation-driven neurodegeneration. This study advances the understanding of TCM's therapeutic contributions to neurodegeneration and positions WGP as a strong candidate for further clinical development in PD treatment.

Oral candidiasis: differentiation of Candida spp strains and antifungal treatments

Introduction: Candida spp is one of the most common yeast species within the oral cavity as a habitual commensal, which in turn is frequently found as an etiological agent of superficial infections. Objective: to characterize aspects related to candidiasis, the acquisition of resistance and its treatment. Method: a review of the available bibliography in databases such as SciELO, Scopus and ClinicalKey was carried out, of which a total of 19 related articles were consulted, empirical methods such as logical history and analysis and synthesis were used. Results: resistance is not only given by the Candida species but also by factors inherent to the host such as the existence of prevalent diseases, massive systemic infections, septicemias, such as immunocompromised patients. The Candida spp species is part of the usual microbiota of living beings, they are opportunistic pathogens that have the capacity to cause superficial, skin or mucosal, or systemic infections. Antifungals used in treatment may be fungistatic or fungicidal. C. albicans predominates in the oral cavity to a greater extent. The species mentioned may be found in the oral cavity and pass into the bloodstream due to host immunodeficiency, as well as other predisposing factors. Conclusions: currently, none of the available antifungals have the characteristics of an ideal antifungal: broad spectrum of action, fungicide, zero resistance rate, multiple administration routes, high capacity for tissue penetration, but without toxicity; and also develop a prophylactic and therapeutic action, without producing adverse effects and maintaining a high effectiveness.

Humanin reduces nucleus pulposus cells ferroptosis to alleviate intervertebral disc degeneration: An in vitro and in vivo study.

Intervertebral disc degeneration (IDD) is a prevalent etiology of low back pain in the global adult population, leading to considerable morbidity and healthcare costs. Existing therapeutic modalities for IDD remain constrained. Ferroptosis in the nucleus pulposus (NP) cells emerges as a pivotal contributor to IDD. Humanin (HN), a mitochondrial-secreted peptide, is intricately linked to age-related maladies and showcases antioxidant, anti-inflammatory, and anti-apoptotic properties. Nonetheless, its precise involvement in IDD remains enigmatic. The expression profile of HN in IDD was scrutinized utilizing human NP cell cultures and an IDD rat model (n=5). The therapeutic efficacy of HN in rats was assessed via MRI and histological evaluation, alongside an exploration of the molecular underpinnings of HN's therapeutic actions in IDD management. This pioneering study unveiled a downregulation of HN expression in IDD patients, a finding corroborated through cell and rat IDD models. Furthermore, it was ascertained that exogenous HN could trigger endogenous HN expression, impede the JAK2/STAT3 and NF-κB pathways, thereby mitigating erastin-induced ferroptosis in NP cells, contingent upon the upregulation of HSP27 expression. Moreover, the study validated the role of HN in preserving mitochondrial homeostasis, curbing mitochondrial reactive oxygen species (mtROS) generation and mtDNA leakage, consequently hindering mtDNA binding to TLR9 and subsequent activation of the NF-κB pathway. Notably, in vivo rat experiments underscored the efficacy of HN treatment in ameliorating IDD progression induced by annulus fibrosus puncture. By assuaging ferroptosis in NP cells, HN exhibits promise as a viable candidate for IDD treatment, capable of impeding disease advancement. The translational potential of this article: This study highlights the importance and effectiveness of HN in alleviating IDD by inhibiting ferroptosis in NP cells. The addition of exogenous HN may represent a potential therapeutic strategy for treating IDD.

Unravelling the Impact: Pulmonary Side Effects of Anti-Seizure Medications

Background: Epilepsy is a chronic brain condition affecting over 50 million people worldwide. Several new anti-seizure medications (ASMs) have been introduced to treat epilepsy in recent decades. Objective: Nearby the specific therapeutic action, ASMs, like other types of pharmacotherapy, can produce various side effects. In this review, we shall analyze the different pharmaceutical classes of ASMs, their mechanism of action, and their interaction with the respiratory system. Methods: This manuscript is based on a retrospective review of English publications indexed by Pubmed, UpToDate and datasheets published by the European Medicines Agency and the Food and Drug Administration (FDA), using various terms reminiscent of ASMs and pulmonary function. Results: ASMs act on organism homeostasis in different ways, acting on lung function directly and indirectly and playing a protective or damaging role. A damaging direct lung involvement ranged from infections, hypersensitivity reactions, and respiratory depression to other structured pulmonary diseases. Meanwhile, a damaging indirect effect, might be constituted by pulmonary artery hypertension. On the other hand, a protective effect might be the expression of developmental processing, decreasing airway remodelling in asthma patients, vascular remodelling in pulmonary hypertension and, nonetheless, anti-inflammatory and immunomodulatory actions. Conclusion: An adequate awareness of ASMs effects on the respiratory system seems essential for better managing frail individuals or/and those predisposed to respiratory disorders to improve our patients' clinical outcomes.

Therapeutic actions of terpenes in neurodegenerative disorders and their correlations with the regulation and remodeling of the extracellular matrix

Therapeutic actions of terpenes in neurodegenerative disorders and their correlations with the regulation and remodeling of the extracellular matrix

Psilocybin-assisted massed cognitive processing therapy for chronic posttraumatic stress disorder: Protocol for an open-label pilot feasibility trial.

Posttraumatic stress disorder (PTSD) affects 3.9% of the general population. While massed cognitive processing therapy (CPT) has demonstrated efficacy in treating chronic PTSD, a substantial proportion of patients still continue to meet PTSD criteria after treatment, highlighting the need for novel therapeutic approaches. Preliminary evidence supports the potential therapeutic action of psilocybin to alleviate PTSD symptoms. This open-label pilot study aims to evaluate the feasibility, tolerability, and preliminary efficacy of a single dose 25 mg psilocybin in combination with one week of massed CPT in patients with chronic PTSD. Fifteen participants with chronic PTSD will undergo 12 CPT sessions, two psilocybin-related psychotherapy sessions, and one psilocybin dosing session over a 7-days period. The primary outcomes are feasibility and tolerability, which will be measured by recruitment rates, withdrawal, data completion, adherence, number and nature of adverse events. Secondary objectives include assessing the preliminary efficacy of psilocybin-assisted CPT in reducing PTSD severity, self-reported treatment outcomes and exploring putative mechanisms of change. Participants will be monitored weekly for 12 weeks post-treatment and passive data relevant to mental health and well-being will be collected using a wearable device. This trial will generate important preliminary data on the use of psilocybin-assisted CPT for treating PTSD. The findings will guide the design of a multi-site, large-scale randomized control trial to more rigorously assess the efficacy of this intervention. De-identified data from this study will be available upon request after publication of the results. This study represents a promising and innovative approach to PTSD treatment, potentially offering an alternative therapeutic option for individuals unresponsive to conventional therapies. ClinicalTrials.gov NCT06386003.