Anti-cancer properties of Sansalvamide A, its derivatives, and analogs: an updated review.

As peptide-based therapies gain recognition for their potential anti-cancer activity, cyclic peptides like Sansalvamide A, a marine-derived cyclic depsipeptide, have emerged as a potential anti-cancer agent due to their potent activity against various cancer types in preclinical studies. This review offers a comprehensive overview of Sansalvamide A, including its sources, structure-activity relationship, and semi-synthetic derivatives. The review also aims to outline the mechanisms through which Sansalvamide A and its analogs exert their anti-proliferative effects and to discuss the need for enhancements in pharmacokinetic profiles for better clinical utility. An extensive literature search was conducted, focusing on studies that detailed the anti-cancer activity of Sansalvamide A, its pharmacokinetics, and mechanistic pathways. Data from both in vitro and in vivo studies were collated and analyzed. Sansalvamide A and its analogs demonstrated significant anti-cancer activity across various cancer models, mediated through Hsp 90 inhibition, Topoisomerase inhibition, and G0/G1 cell cycle arrest. However, their pharmacokinetic properties were identified as a significant limitation, requiring improvement for effective clinical translation. Despite its notable anti-cancer effects, the utility of Sansalvamide A is currently limited by its pharmacokinetic characteristics. Therefore, while Sansalvamide A exhibits promise as an anti-cancer agent, there is a compelling need for further clinical and toxicological studies and optimization of its pharmacokinetic profile to fully exploit its therapeutic potential alongside modern cancer therapies.

Nutritional Sources and Anticancer Potential of Phenethyl Isothiocyanate: Molecular Mechanisms and Therapeutic Insights.

Phenethyl isothiocyanate (PEITC), a compound derived from cruciferous vegetables, has garnered attention for its anticancer properties. This review synthesizes existing research on PEITC, focusing on its mechanisms of action in combatting cancer. PEITC has been found to be effective against various cancer types, such as breast, prostate, lung, colon, and pancreatic cancers. Its anticancer activities are mediated through several mechanisms, including the induction of apoptosis (programmed cell death), inhibition of cell proliferation, suppression of angiogenesis (formation of new blood vessels that feed tumors), and reduction of metastasis (spread of cancer cells to new areas). PEITC targets crucial cellular signaling pathways involved in cancer progression, notably the Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB), Protein Kinase B (Akt), and Mitogen-Activated Protein Kinase (MAPK) pathways. These findings suggest PEITC's potential as a therapeutic agent against cancer. However, further research is necessary to determine the optimal dosage, understand its bioavailability, and assess potential side effects. This will be crucial for developing PEITC-based treatments that are both effective and safe for clinical use in cancer therapy.

Polymeric nanoparticles decorated with fragmented chitosan as modulation systems for neuronal drug uptake.

This study aimed to modify chitosan (CS) by gamma irradiation and use it as a surface coating of nanoparticles (NPs) fabricated of poly lactic-co-glycolic acid (PLGA) to create mostly biocompatible nanosystems that can transport drugs to neurons. Gamma irradiation produced irradiated CS (CSγ) with a very low molecular weight (15.2-19.2 kDa). Coating NPs-PLGA with CSγ caused significant changes in their Z potential, making it slightly positive (from -21.7 ± 2.8 mV to +7.1 ± 2.3 mV) and in their particle size (184.4 0.4 ± 7.9 nm to 211.9 ± 14.04 nm). However, these changes were more pronounced in NPs coated with non-irradiated CS (Z potential = +54.0 ± 1.43 mV, size = 348.1 ± 16.44 nm). NPs coated with CSγ presented lower cytotoxicity and similar internalization levels in SH-SY5Y neuronal cells than NPs coated with non-irradiated CS, suggesting higher biocompatibility. Highly biocompatible NPs are desirable as nanocarriers to deliver drugs to the brain, as they help maintain the structure and function of the blood-brain barrier. Therefore, the NPs developed in this study could be evaluated as drug-delivery systems for treating brain diseases.

Arnicolide D: a multi-targeted anticancer sesquiterpene lactone-preclinical efficacy and mechanistic insights.

Arnicolide D, a potent sesquiterpene lactone from Centipeda minima, has emerged as a promising anticancer candidate, demonstrating significant efficacy in inhibiting cancer cell proliferation, inducing apoptosis, and suppressing metastasis across various cancer models. This comprehensive study delves into the molecular underpinnings of Arnicolide D's anticancer actions, emphasizing its impact on key signaling pathways such as PI3K/AKT/mTOR and STAT3, and its role in modulating cell cycle and survival mechanisms. Quantitative data from preclinical studies reveal Arnicolide D's dose-dependent cytotoxicity against cancer cell lines, including nasopharyngeal carcinoma, triple-negative breast cancer, and human colon carcinoma, showcasing its broad-spectrum anticancer potential. Given its multifaceted mechanisms and preclinical efficacy, Arnicolide D warrants further investigation in clinical settings to validate its therapeutic utility against cancer. The evidence presented underscores the need for rigorous pharmacokinetic and toxicological studies to establish safe dosing parameters for future clinical trials.

Neuroprotective and anti-inflammatory effects of curcumin in Alzheimer's disease: Targeting neuroinflammation strategies.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of amyloid-beta plaques and neurofibrillary tangles, leading to neuronal loss. Curcumin, a polyphenolic compound derived from Curcuma longa, has shown potential neuroprotective effects due to its anti-inflammatory and antioxidant properties. This review aims to synthesize current preclinical data on the anti-neuroinflammatory mechanisms of curcumin in the context of AD, addressing its pharmacokinetics, bioavailability, and potential as a therapeutic adjunct. An exhaustive literature search was conducted, focusing on recent studies within the last 10 years related to curcumin's impact on neuroinflammation and its neuroprotective role in AD. The review methodology included sourcing articles from specialized databases using specific medical subject headings terms to ensure precision and relevance. Curcumin demonstrates significant neuroprotective properties by modulating neuroinflammatory pathways, scavenging reactive oxygen species, and inhibiting the production of pro-inflammatory cytokines. Despite its potential, challenges remain regarding its limited bioavailability and the scarcity of comprehensive human clinical trials. Curcumin emerges as a promising therapeutic adjunct in AD due to its multimodal neuroprotective benefits. However, further research is required to overcome challenges related to bioavailability and to establish effective dosing regimens in human subjects. Developing novel delivery systems and formulations may enhance curcumin's therapeutic potential in AD treatment.

New insights into the anticancer therapeutic potential of icaritin and its synthetic derivatives.

Icaritin is a natural prenylated flavonoid derived from the Chinese herb Epimedium. The compound has shown antitumor effects in various cancers, especially hepatocellular carcinoma (HCC). Icaritin exerts its anticancer activity by modulating multiple signaling pathways, such as IL-6/JAK/STAT3, ER-α36, and NF-κB, affecting the tumor microenvironment and immune system. Several clinical trials have evaluated the safety and efficacy of icaritin in advanced HCC patients with poor prognoses, who are unsuitable for conventional therapies. The results have demonstrated that icaritin can improve survival, delay progression, and produce clinical benefits in these patients, with a favorable safety profile and minimal adverse events. Moreover, icaritin can enhance the antitumor immune response by regulating the function and phenotype of various immune cells, such as CD8+ T cells, MDSCs, neutrophils, and macrophages. These findings suggest that icaritin is a promising candidate for immunotherapy in HCC and other cancers. However, further studies are needed to elucidate the molecular mechanisms and optimal dosing regimens of icaritin and its potential synergistic effects with other agents. Therefore, this comprehensive review of the scientific literature aims to summarize advances in the knowledge of icaritin in preclinical and clinical studies as well as the pharmacokinetic, metabolism, toxicity, and mechanisms action to recognize the main challenge, gaps, and opportunities to develop a medication that cancer patients can use. Thus, our main objective was to clarify the current state of icaritin for use as an anticancer drug.

Real-world prostate-specific antigen reduction and survival outcomes of metastatic hormone-sensitive prostate cancer patients treated with apalutamide: An observational, retrospective, and multicentre study.

Background: Metastatic hormone-sensitive prostate cancer (mHSPC) treatment has changed drastically during the last years with the emergence of androgen receptor-targeted agents (ARTAs). ARTA combined with androgen deprivation therapy has demonstrated better oncological and survival outcomes in these patients. However, the optimal choice among different ARTAs remains uncertain due to their analogous efficacy. Objectives: The objective of this study was to describe prostate-specific antigen (PSA) response and oncological outcomes of patients with mHSPC treated with apalutamide. Material and methods: Medical records from three different hospitals in Spain were used to conduct this study. Patients diagnosed with mHSPC and under apalutamide treatment were included between March 2021 and January 2023. Data regarding PSA response, overall survival (OS), and radiographic progression-free survival (rPFS) were collected and stratified by metastasis volume, timing, and stating. Results: 193 patients were included; 34.2% of patients were de novo mHSPC, and the majority was classified as m1b. The 18-month OS and rPFS were 92.5% and 88.9%, respectively. Patients with PSA levels ≤0.2 ng/ml showcased an 18-month OS rate of 98.7%, contrasting with 65.3% for those with PSA >0.2 ng/ml. Similar trends emerged for rPFS (97.4% and 53.7%, respectively). When differentiating between low-volume and high-volume metastasis, the OS rate stood at 98.4% and 80.7%, respectively, while the rPFS rates were 93% and 81.6%, respectively. No significant differences were found between groups stratified by metastasis timing. Conclusion: This real-world study on patients with mHSPC treated with apalutamide plus androgen deprivation therapy revealed robust oncological outcomes, aligning with the emerging evidence. The study's hallmark finding highlights the significance of rapid and deep PSA response as a predictor of improved oncological and survival outcomes.

Preparation of xyloglucan-grafted poly(N-hydroxyethyl acrylamide) copolymer by free-radical polymerization for in vitro evaluation of human dermal fibroblasts.

Xyloglucan is a rigid polysaccharide that belongs to the carbohydrate family. This hemicellulose compound has been widely used in biomedical research because of its pseudoplastic, mucoadhesive, mucomimetic, and biocompatibility properties. Xyloglucan is a polyose with no amino groups in its structure, which also limits its range of applications. It is still unknown whether grafting hydrophilic monomers onto xyloglucan can produce derivatives that overcome these shortcomings. This work aimed to prepare the first copolymers in which N-hydroxyethyl acrylamide is grafted onto tamarind xyloglucan by free-radical polymerization. The biocompatibility of these structures in vitro was evaluated using human dermal fibroblasts. Gamma radiation-induced graft polymerization was employed as an initiator by varying the radiation dose from 5-25 kGy. The structure of the graft copolymer, Xy-g-poly(N-hydroxyethyl acrylamide), was verified by thermal analysis, Fourier transform infrared spectroscopy, and nuclear magnetic resonance spectroscopy. The findings indicate that the degree of grafting and the cytotoxicity/viability of the xyloglucan-based copolymer were independent of dose. Notably, the grafted galactoxyloglucan exhibited efficient support for human dermal fibroblasts, showing heightened proliferative capacity and superior migration capabilities compared to the unmodified polymer. This copolymer might have the potential to be used in skin tissue engineering.

8-OxoG-Dependent Regulation of Global Protein Responses Leads to Mutagenesis and Stress Survival in Bacillus subtilis.

The guanine oxidized (GO) system of Bacillus subtilis, composed of the YtkD (MutT), MutM and MutY proteins, counteracts the cytotoxic and genotoxic effects of the oxidized nucleobase 8-OxoG. Here, we report that in growing B. subtilis cells, the genetic inactivation of GO system potentiated mutagenesis (HPM), and subsequent hyperresistance, contributes to the damaging effects of hydrogen peroxide (H2O2) (HPHR). The mechanism(s) that connect the accumulation of the mutagenic lesion 8-OxoG with the ability of B. subtilis to evolve and survive the noxious effects of oxidative stress were dissected. Genetic and biochemical evidence indicated that the synthesis of KatA was exacerbated, in a PerR-independent manner, and the transcriptional coupling repair factor, Mfd, contributed to HPHR and HPM of the ΔGO strain. Moreover, these phenotypes are associated with wider pleiotropic effects, as revealed by a global proteome analysis. The inactivation of the GO system results in the upregulated production of KatA, and it reprograms the synthesis of the proteins involved in distinct types of cellular stress; this has a direct impact on (i) cysteine catabolism, (ii) the synthesis of iron-sulfur clusters, (iii) the reorganization of cell wall architecture, (iv) the activation of AhpC/AhpF-independent organic peroxide resistance, and (v) increased resistance to transcription-acting antibiotics. Therefore, to contend with the cytotoxic and genotoxic effects derived from the accumulation of 8-OxoG, B. subtilis activates the synthesis of proteins belonging to transcriptional regulons that respond to a wide, diverse range of cell stressors.

Long-Term Effect of Maternal Antioxidant Supplementation on the Lipid Profile of the Progeny According to the Sow's Parity Number.

Pig feeding prior to the extensive fattening phase might affect the final lipid profile and product quality. This study evaluates how maternal supplementation with vitamin E (VITE) (100 mg/kg), hydroxytyrosol (HXT) (1.5 mg/kg), or combined administration (VE + HXT) affects the piglet's plasma and tissues' fatty acid profiles and lipid stability according to the sow's parity number (PN), as well as the possible changes to the lipid profile after extensive feeding. The sows' PN affected the total fatty acid profile of plasma, muscle, and liver of piglets, with lower Δ-9 and Δ-6 desaturase indices but higher Δ-5 in those from primiparous (P) than multiparous (M) sows. Dietary VITE was more effective at decreasing C16:0 and saturated fatty acids in the muscle of piglets born from M than P sows, and modified the liver phospholipids in a different way. Sows' supplementation with HXT increased C18:2n-6 in triglycerides and polyunsaturated fatty acids (PUFA) in muscle phospholipids. In the liver, HXT supplementation also increased free-PUFA and free-n-3 fatty acids. However, lipid oxidation of piglets' tissues was not affected by the antioxidant supplementation, and it was higher in the livers of piglets born from M sows. The fatty acid profile in the muscle of pigs after extensive feeding was not affected by the PN, but it was by the sows' antioxidant supplementation, with positive effects on quality by both compounds.

Inhibition of Chk1 stimulates cytotoxic action of platinum-based drugs and TRAIL combination in human prostate cancer cells.

Checkpoint kinase 1 (Chk1) plays an important role in regulation of the cell cycle, DNA damage response and cell death, and represents an attractive target in anticancer therapy. Small-molecule inhibitors of Chk1 have been intensively investigated either as single agents or in combination with various chemotherapeutic drugs and they can enhance the chemosensitivity of numerous tumor types. Here we newly demonstrate that pharmacological inhibition of Chk1 using potent and selective inhibitor SCH900776, currently profiled in phase II clinical trials, significantly enhances cytotoxic effects of the combination of platinum-based drugs (cisplatin or LA-12) and TRAIL (tumor necrosis factor-related apoptosis inducing ligand) in human prostate cancer cells. The specific role of Chk1 in the drug combination-induced cytotoxicity was confirmed by siRNA-mediated silencing of this kinase. Using RNAi-based methods we also showed the importance of Bak-dependent mitochondrial apoptotic pathway in the combined anticancer action of SCH900776, cisplatin and TRAIL. The triple drug combination-induced cytotoxicity was partially enhanced by siRNA-mediated Mcl-1 silencing. Our findings suggest that targeting Chk1 may be used as an efficient strategy for sensitization of prostate cancer cells to killing action of platinum-based chemotherapeutic drugs and TRAIL.

Advances in chitosan and chitosan derivatives for biomedical applications in tissue engineering: An updated review.

In recent years, chitosan (CS) has received much attention as a functional biopolymer for various applications, especially in the biomedical field. It is a natural polysaccharide created by the chemical deacetylation of chitin (CT) that is nontoxic, biocompatible, and biodegradable. This natural polymer is difficult to process; however, chemical modification of the CS backbone allows improved use of functional derivatives. CS and its derivatives are used to prepare hydrogels, membranes, scaffolds, fibers, foams, and sponges, primarily for regenerative medicine. Tissue engineering (TE), currently one of the fastest-growing fields in the life sciences, primarily aims to restore or replace lost or damaged organs and tissues using supports that, combined with cells and biomolecules, generate new tissue. In this sense, the growing interest in the application of biomaterials based on CS and some of its derivatives is justifiable. This review aims to summarize the most important recent advances in developing biomaterials based on CS and its derivatives and to study their synthesis, characterization, and applications in the biomedical field, especially in the TE area.

Fosfatriclaben, a prodrug of triclabendazole: Preparation, stability, and fasciolicidal activity of three new intramuscular formulations.

In this study, we present the preparation, stability, and in vivo fasciolicidal activity of three new intramuscular formulations in sheep of a prodrug based on triclabendazole, named fosfatriclaben. The new formulations were ready-to-use aqueous solutions with volumes recommended for intramuscular administration in sheep. The use of poloxamers (P-407 and P-188) and polysorbates (PS-20 and PS-80) in the new formulations improved the aqueous solubility of fosfatriclaben by 8-fold at pH 7.4. High-performance liquid chromatography with UV detection was used to evaluate the stability of fosfatriclaben in the three formulations. High recovery (> 90%) of fosfatriclaben was found for all formulations after exposure at 57 ± 2 °C for 50 h. The three intramuscular formulations showed high fasciolicidal activity at a dose of 6 mg/kg, which was equivalent to the triclabendazole content. The fasciolicidal activity of fosfatriclaben was similar to commercial oral (Fasimec®) and intramuscular (Endovet®) triclabendazole formulations at a dose of 12 mg/kg. In the in vivo experiments, all formulations administered intramuscularly reduced egg excretion by 100%, and formulations F1, F2, and F3 presented fasciolicidal activities of 100%, 100%, and 99.6%, respectively.

Living with depression and diabetes: A qualitative study in Bangladesh and Pakistan.

Diabetes and depression are both serious health conditions. While their relationship is bidirectional and each condition adversely affects outcomes for the other, they are treated separately. In low and middle income countries, such as Bangladesh and Pakistan, health systems are already stretched and the integration of diabetes and depression care is rarely a priority. Within this context through interviews with patients, healthcare workers and policy makers the study explored: lived experiences of people living with depression and diabetes, current practice in mental health and diabetes care and barriers and perspectives on integrating a brief psychological therapy into diabetes care. The findings of the study included: differing patient and practitioner understandings of distress/depression, high levels of stigma for mental health and a lack of awareness and training on treating depression. While it was apparent there is a need for more holistic care and the concept of a brief psychological intervention appeared acceptable to participants, many logistical barriers to integrating a mental health intervention into diabetes care were identified. The study highlights the importance of context and of recognising drivers and understandings of distress when planning for more integrated mental and physical health services, and specifically when adapting and implementing a new intervention into existing services.

Optimize the parameters for the synthesis by the ionic gelation technique, purification, and freeze-drying of chitosan-sodium tripolyphosphate nanoparticles for biomedical purposes.

BACKGROUND: Polymeric nanoparticles can be used for wound closure and therapeutic compound delivery, among other biomedical applications. Although there are several nanoparticle obtention methods, it is crucial to know the adequate parameters to achieve better results. Therefore, the objective of this study was to optimize the parameters for the synthesis, purification, and freeze-drying of chitosan nanoparticles. We evaluated the conditions of agitation speed, anion addition time, solution pH, and chitosan and sodium tripolyphosphate concentration. RESULTS: Chitosan nanoparticles presented an average particle size of 172.8 ± 3.937 nm, PDI of 0.166 ± 0.008, and zeta potential of 25.00 ± 0.79 mV, at the concentration of 0.1% sodium tripolyphosphate and chitosan (pH 5.5), with a dripping time of 2 min at 500 rpm. The most representative factor during nanoparticle fabrication was the pH of the chitosan solution, generating significant changes in particle size and polydispersity index. The observed behavior is attributed to the possible excess of sodium tripolyphosphate during synthesis. We added the surfactants poloxamer 188 and polysorbate 80 to evaluate the stability improvement during purification (centrifugation or dialysis). These surfactants decreased coalescence between nanoparticles, especially during purification. The centrifugation increased the zeta potential to 40.8-56.2 mV values, while the dialyzed samples led to smaller particle sizes (152-184 nm). Finally, freeze-drying of the chitosan nanoparticles proceeded using two cryoprotectants, trehalose and sucrose. Both adequately protected the system during the process, and the sugar concentration depended on the purification process. CONCLUSIONS: In Conclusion, we must consider each surfactant's benefits in formulations for selecting the most suitable. Also, it is necessary to do more studies with the molecule to load. At the same time, the use of sucrose and trehalose generates adequate protection against the freeze-drying process, even at a 5% w/v concentration. However, adjusting the percentage concentration by weight must be made to work with the CS-TPP NPs purified by dialysis.

Pharmacological properties of mangiferin: bioavailability, mechanisms of action and clinical perspectives.

This review aims to provide an in-depth analysis of the pharmacological properties of mangiferin, focusing primarily on its bioavailability and mechanisms of action, and its potential therapeutic applications, especially in the context of chronic diseases. We conducted a comprehensive examination of in vitro and in vivo studies, as well as clinical trials involving mangiferin or plant extracts containing mangiferin. The primary source of mangiferin is Mangifera indica, but it's also found in other plant species from the families Anacardiaceae, Gentianaceae, and Iridaceae. Mangiferin has exhibited a myriad of therapeutic properties, presenting itself as a promising candidate for treating various chronic conditions including neurodegenerative disorders, cardiovascular diseases, renal and pulmonary diseases, diabetes, and obesity. Despite the promising results showcased in many in vitro studies and certain animal studies, the application of mangiferin has been limited due to its poor solubility, absorption, and overall bioavailability. Mangiferin offers significant therapeutic potential in treating a spectrum of chronic diseases, as evidenced by both in vitro and clinical trials. However, the challenges concerning its bioavailability necessitate further research, particularly in optimizing its delivery and absorption, to harness its full medicinal potential. This review serves as a comprehensive update on the health-promoting and therapeutic activities of mangiferin.

Dopamine D3 receptor modulates D2 receptor effects on cAMP and GABA release at striatopallidal terminals-Modulation by the Ca2+-Calmodulin-CaMKII system.

Dopamine D2 receptor (D2R) is expressed in striatopallidal neurons and decreases forskolin-stimulated cyclic adenine monophosphate (cAMP) accumulation and gamma-aminobutyric acid (GABA) release. Dopamine D3 receptor (D3R) mRNA is expressed in a population of striatal D2R-expressing neurons. Also, D3R protein and binding have been reported in the neuropil of globus pallidus. We explore whether D2R and D3R colocalize in striatopallidal terminals and whether D3R modulates the D2R effect on forskolin-stimulated [3H]cAMP accumulation in pallidal synaptosomes and high K+ stimulated-[3H]GABA release in pallidal slices. Previous reports in heterologous systems indicate that calmodulin (CaM) and CaMKII modulate D2R and D3R functions; thus, we study whether this system regulates its functional interaction. D2R immunoprecipitates with CaM, and pretreatment with ophiobolin A or depolarization of synaptosomes with 15 mM of K+ decreases it. Both treatments increase the D2R inhibition of forskolin-stimulated [3H]cAMP accumulation when activated with quinpirole, indicating a negative modulation of CaM on D2R function. Quinpirole also activates D3R, potentiating D2R inhibition of cAMP accumulation in the ophiobolin A-treated synaptosomes. D2R and D3R immunoprecipitate in pallidal synaptosomes and decrease after the kainic acid striatal lesion, indicating the striatal origin of the presynaptic receptors. CaM-kinase II alfa (CaMKIIα) immunoprecipitates with D3R and increases after high K+ depolarization. In the presence of KN62, a CaMKIIα blocker, D3R potentiates D2R effects on cAMP accumulation in depolarized synaptosomes and GABA release in pallidal slices, indicating D3R function regulation by CaMKIIα. Our data indicate that D3R potentiates the D2R effect on cAMP accumulation and GABA release at pallidal terminals, an interaction regulated by the CaM-CaMKIIα system.

Development of a Polymeric Pharmacological Nanocarrier System as a Potential Therapy for Spinocerebellar Ataxia Type 7.

Spinocerebellar ataxia type 7 (SCA7) is an autosomal-dominant inherited disease characterized by progressive ataxia and retinal degeneration. SCA7 belongs to a group of neurodegenerative diseases caused by an expanded CAG repeat in the disease-causing gene, resulting in aberrant polyglutamine (polyQ) protein synthesis. PolyQ ataxin-7 is prone to aggregate in intracellular inclusions, perturbing cellular processes leading to neuronal death in specific regions of the central nervous system (CNS). Currently, there is no treatment for SCA7; however, a promising approach successfully applied to other polyQ diseases involves the clearance of polyQ protein aggregates through pharmacological activation of autophagy. Nonetheless, the blood-brain barrier (BBB) poses a challenge for delivering drugs to the CNS, limiting treatment effectiveness. This study aimed to develop a polymeric nanocarrier system to deliver therapeutic agents across the BBB into the CNS. We prepared poly(lactic-co-glycolic acid) nanoparticles (NPs) modified with Poloxamer188 and loaded with rapamycin to enable NPs to activate autophagy. We demonstrated that these rapamycin-loaded NPs were successfully taken up by neuronal and glial cells, demonstrating high biocompatibility without adverse effects. Remarkably, rapamycin-loaded NPs effectively cleared mutant ataxin-7 aggregates in a SCA7 glial cell model, highlighting their potential as a therapeutic approach to fight SCA7 and other polyQ diseases.

Advances in the treatment of autosomal recessive congenital ichthyosis, a look towards the repositioning of drugs.

Autosomal recessive congenital ichthyoses (ARCI) are a skin pathology due to genetic causes characterized by a variable degree of desquamation, accompanied by erythema. The degree of symptoms is variable, different altered genes are involved, and the symptoms drastically affect patients' quality of life. Topical treatments are a first-choice strategy due to their ease of application and cost; however, enteral administration of retinoids offers greater efficacy, although with certain limitations. Despite the treatment alternatives, ARCI will persist throughout life, disabling people. Therefore, the search for new treatments always remains necessary. Especially repositioning drugs could be a short-term alternative to new affordable treatments for patients. Taking advantage of extensive knowledge of known drugs or biologics could ensure more accessible and possibly lower-cost treatments. This review briefly and concisely addresses possible repositioning strategies with drugs and biologics for ichthyosis.

Novel ultra-stretchable and self-healing crosslinked poly (ethylene oxide)-cationic guar gum hydrogel.

Hydrogels are three-dimensional structures with specific features that render them useful for biomedical applications, such as tissue engineering scaffolds, drug delivery systems, and wound dressings. In recent years, there has been a significant increase in the search for improved mechanical properties of hydrogels derived from natural products to extend their applications in various fields, and there are different methods to obtain strengthened hydrogels. Cationic guar gum has physicochemical properties that allow it to interact with other polymers and generate hydrogels. This study aimed to develop an ultra-stretchable and self-healing hydrogel, evaluating the influence of adding PolyOX [poly(ethylene oxide)] on the mechanical properties and the interaction with cationic guar gum for potential tissue engineering applications. We found that variations in PolyOX concentrations and pH changes influenced the mechanical properties of cationic guar gum hydrogels. After optimization experiments, we obtained a novel hydrogel, which was semi-crystalline, highly stretchable, and with an extensibility area of approximately 400 cm2, representing a 33-fold increase compared to the hydrogel before being extended. Moreover, the hydrogel presented a recovery of 96.8% after the self-healing process and a viscosity of 153,347 ± 4,662 cP. Therefore, this novel hydrogel exhibited optimal mechanical and chemical properties and could be suitable for a broad range of applications in different fields, such as tissue engineering, drug delivery, or food storage.