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Spinocerebellar ataxia type 7 (SCA7) is a rare genetic disease characterized by progressive cerebellar syndrome and macular degeneration. In a previous study, we clinically and genetically characterized a group of Mexican patients, which represented one of the largest cohorts of SCA7 patients worldwide and demonstrated that all patients had a unique genetic origin. Our laboratory developed a program for the diagnosis, medical care, and long-term follow-up of these patients living in Veracruz State, and in this report, we present an update to this research, covering 2013 to 2024. So far, we identified 172 SCA7 carriers, with a few cases outside Veracruz, and our data support that the length of the CAG repeat tract mainly determines disease severity and life expectancy, and accordingly, we define three different phenotypes, early-onset (EO), classical-onset (CO), and late-onset (LO), with EO patients showing the lowest life expectancy. Furthermore, we found that parental transmission of mutant alleles leads to increased CAG repeat instability, compared to maternal ones. Interestingly, a haplotype analysis revealed that patients outside Veracruz may have different genetic origins. In conclusion, longitudinal observations of SCA7 patients provide insight into the natural history of SCA7 and help to design strategies for diagnosis, genetic counseling, physical rehabilitation, and therapeutic alternatives. [ABSTRACT FROM AUTHOR]

Lithium, a natural element, has been employed as a mental stabilizer in psychiatric treatments; however, some reports indicate it has an anticancer effect, prompting the consideration of repurposing lithium for cancer treatment. The potential anticancer use of lithium may depend on its form (salt type) and the type of cancer cells targeted. Little is known about the effects of Li2CO3 or LiCl on cancer cells, so we focused on exploring their effects on proliferation, apoptosis, migration, and cell cycle as part of the hallmarks of cancer. Firstly, we established the IC50 values on HeLa, SiHa, and HaCaT cells with LiCl and Li2CO3 and determined by crystal violet that cell proliferation was time-dependent in the three cell lines (IC50 values for LiCl were 23.43 mM for SiHa, 23.14 mM for HeLa, and 15.10 mM for HaCaT cells, while the IC50 values for Li2CO3 were 20.57 mM for SiHa, 11.52 mM for HeLa, and 10.52 mM for HaCaT cells.) Our findings indicate that Li2CO3 and LiCl induce DNA fragmentation and caspase-independent apoptosis, as shown by TUNEL, Western Blot, and Annexin V/IP assay by flow cytometry. Also, cell cycle analysis showed that LiCl and Li2CO3 arrested the cervical cancer cells at the G1 phase. Moreover, lithium salts displayed an anti-migratory effect on the three cell lines observed by the wound-healing assay. All these findings imply the viable anticancer effect of lithium salts by targeting several of the hallmarks of cancer. [ABSTRACT FROM AUTHOR]

Delayed wound healing increases the wound's vulnerability to possible infections, which may have lethal outcomes. The treatments available can be effective, but the urgency is not fully encompassed. The drug repositioning strategy proposes effective alternatives for enhancing medical therapies for chronic diseases. Likewise, applying wound dressings as biodegradable membranes is extremely attractive due to their ease of application, therapeutic effectiveness, and feasibility in industrial manufacturing. This article aims to demonstrate the pleiotropic effects during insulin repositioning in wound closure by employing a biopolymeric membrane-type formulation with insulin. We prepared biopolymeric membranes with sodium alginate cross-linked with calcium chloride, supported in a mixture of xanthan gum and guar gum, and plasticized with glycerol and sorbitol. Human insulin was combined with poloxamer 188 as a protein stabilizing agent. Our investigation encompassed physicochemical and mechanical characterization, antioxidant and biological activity through antibacterial tests, cell viability assessments, and scratch assays as an in vitro and in vivo wound model. We demonstrated that our biopolymeric insulin membranes exhibited adequate manipulation and suitable mechanical resistance, transparency, high swelling capability (1100%), and 30% antioxidant activity. Furthermore, they exhibited antibacterial activity (growth inhibition of S. aureus at 85% and P. aeruginosa at 75%, respectively), and insulin promoted wound closure in vitro with a 5.5-fold increase and 72% closure at 24 h. Also, insulin promoted in vivo wound closure with a 3.2-fold increase and 92% closure at 10 days compared with the groups without insulin, and this is the first report that demonstrates this therapeutic effect with two administrations of 0.7 IU. In conclusion, we developed a multifunctional insulin-loaded biopolymeric membrane in this study, with the main activity derived from insulin's role in wound closure and antioxidant activity, augmented by the antimicrobial effect attributed to the polymer poloxamer 188. The synergistic combination of excipients enhances its usefulness and highlights our innovation as a promising material in wound healing materials. [ABSTRACT FROM AUTHOR]

Cancer is a major global health challenge that affects every nation and accounts for a large portion of the worldwide disease burden. Furthermore, cancer cases will rise significantly in the next few decades. The Food and Drug Administration has approved more than 600 drugs for treating diverse types of cancer. However, many conventional anticancer medications cause side effects, and drug resistance develops as the treatment proceeds with a concomitant impact on patients' quality of life. Thus, exploring natural products with antitumor properties and nontoxic action mechanisms is essential. Ginger (Zingiber officinale Roscoe) rhizome has a long history of use in traditional medicine, and it contains biologically active compounds, gingerols and shogaols. The main ginger shogaol is 6‐shogaol, whose concentration dramatically increases during the processing of ginger, primarily due to the heat‐induced conversion of 6‐gingerol. Some studies have demonstrated that 6‐shogaol possesses biological and pharmacological properties, such as antioxidant, anti‐inflammatory, and anticancer activities. The mechanism of action of 6‐shogaol as an anticancer drug includes induction of paraptosis, induction of apoptosis, increase in the production of reactive oxygen species, induction of autophagy, and the inhibition of AKT/mTOR signaling. Despite this knowledge, the mechanism of action of 6‐shogaol is not fully understood, and the scientific data on its therapeutic dose, safety, and toxicity are not entirely described. This review article examines the potential of 6‐shogaol as an anticancer drug, addressing the limitations of current medications; it covers 6‐shogaol's attributes, mechanism of action in cancer cells, and opportunities for future research. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The emergence of bacterial strains displaying resistance to the currently available antibiotics is a critical global concern. These resilient bacteria can form biofilms that play a pivotal role in the failure of bacterial infection treatments as antibiotics struggle to penetrate all biofilm regions. Consequently, eradicating bacteria residing within biofilms becomes considerably more challenging than their planktonic counterparts, leading to persistent and chronic infections. Among various approaches explored, essential oils loaded in nanoparticles based on biopolymers have emerged, promising strategies that enhance bioavailability and biological activities, minimize side effects, and control release through regulated pharmacokinetics. Different available reviews analyze nanosystems and essential oils; however, usually, their main goal is the analysis of their antimicrobial properties, and progress in biofilm combat is rarely discussed, or it is not the primary objective. This review aims to provide a global vision of biofilm conformation and describes mechanisms of action attributed to each EO. Furthermore, we present a comprehensive overview of the latest developments in biopolymeric nanoparticles research, especially in chitosan- and zein-based nanosystems, targeting multidrug-resistant bacteria in both their sessile and biofilm forms, which will help to design precise strategies for combating biofilms. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Simple Summary: The global population is growing at higher rates and food production must grow at a similar rate. Aquaculture is one the most important sources of protein for human consumption, and its sustainable growth is of vital importance. The Chilean salmon industry exported 751,000 metric tons of fish in 2022; however, many diseases affected the production of these products. Piscirickettsia salmonis is the main bacteria infecting salmon in Chile, causing 10% of losses. Currently, no successful treatment exists against this bacterium. Quillaja saponins are secondary metabolites with biological applications, and have shown antiviral, antifungal, and antibacterial properties, as well as acting as immunomodulators. Here, we tested the effect of quillaja extracts in protecting against P. salmonis infection. These products were applied as a supplement in the feed, and displayed in different model trials protective effect against the infection. All treated groups showed a higher survival percentage in comparison to the control group. In addition, quillaja extracts were able to increase the immune responses measured throughout different cytokines. Finally, in a pilot-scale trial, it was observed that fish fed with quillaja saponins exhibited a reduction in mortality and a reduction in the need for antibiotic treatment. These results represent evidence that quillaja saponins are a potential natural non-pharmacological strategy to prevent intracellular infections. Piscirickettsiosis, the main infectious disease affecting salmon farming in Chile, still has no efficient control measures. Piscirickettsia salmonis is a facultative intracellular bacterium that can survive and replicate within the host macrophages, evading the immune response. Triterpenic saponins obtained from the Quillaja saponaria tree have been widely studied, and have been shown to be immunomodulatory agents, suitable for feed and vaccine applications for veterinary and human uses. The impact of the oral administration of two extracts of Quillaja saponins on the infection of P. salmonis in Salmo salar and the corresponding gene expressions of immunomarkers were studied under three in vivo models. In the intraperitoneal challenge model, the group fed with Quillaja extracts showed lower mortality (29.1% treated vs. 37.5% control). Similar results were obtained in the cohabitation model trial (36.3% vs. 60.0%). In the commercial pilot trial, the results showed a significant reduction of 71.3% in mortality caused by P. salmonis (0.51% vs. 1.78%) and antibiotic use (reduction of 66.6% compared to untreated control). Also, Quillaja extracts significantly modulated the expression of IFN-II and CD8. These results represent evidence supporting the future use of purified Quillaja extracts as a natural non-pharmacological strategy for the prevention and control of P. salmonis infections in salmon. [ABSTRACT FROM AUTHOR]

Lamellar ichthyosis (LI) is a genodermatosis that injures the structure and function of the skin, affecting the appearance and self-esteem of patients, which may seriously impair their mental health and quality of life. In the present study, we determined anxiety, depression, and suicidal risk levels in patients with LI through the Beck anxiety and depression inventories (BAI and DBI-II, respectively) and the SAD PERSONS scale (SPS). We observed that anxiety, depression, and suicidal ideation were strongly associated with the LI (Cramér's V = 0.429, 0.594, and 0.462, respectively). Furthermore, patients with LI showed a significant increase in the scores of anxiety, depression, and suicidal risk (p = 0.011, <0.001, and 0.001, respectively) compared to individuals without the disease. Additionally, the suicide risk increased even more in patients who presented comorbidity of anxiety and depression than in patients who presented only anxiety or depression (p = 0.02). Similarly, the increase in the BAI scores correlated with the score observed on the SPS. Our results indicate that patients with LI have higher levels of anxiety and depression compared to individuals without the disease, which could be associated with suicidal risk. Therefore, the collaborative involvement of skin and mental health professionals is necessary to manage patients with LI appropriately. We believe that psychiatric studies and individual evaluations must be performed in LI patients to determine a treatment that, in addition to reducing skin symptoms, focuses on reducing the levels of depression and anxiety and improving the quality of life to reduce the risk of suicide. [ABSTRACT FROM AUTHOR]

Being the first or second cause of death worldwide, cancer represents the most significant clinical, social, and financial burden of any human illness. Despite recent progresses in cancer diagnosis and management, traditional cancer chemotherapies have shown several adverse side effects and loss of potency due to increased resistance. As a result, one of the current approaches is on with the search of bioactive anticancer compounds from natural sources. Neopeltolide is a marine-derived macrolide isolated from deep-water sponges collected off Jamaica's north coast. Its mechanism of action is still under research but represents a potentially promising novel drug for cancer therapy. In this review, we first illustrate the general structural characterization of neopeltolide, the semisynthetic derivatives, and current medical applications. In addition, we reviewed its anticancer properties, primarily based on in vitro studies, and the possible clinical trials. Finally, we summarize the recent progress in the mechanism of antitumor action of neopeltolide. According to the information presented, we identified two principal challenges in the research, i) the effective dose which acts neopeltolide as an anticancer compound, and ii) to unequivocally establish the mechanism of action by which the compound exerts its antiproliferative effect. [ABSTRACT FROM AUTHOR]

This work proposes a combination of polyethylene glycol 400 (PEG) and trehalose as a surface modification approach to enhance PLGA-based nanoparticles as a drug carrier for neurons. PEG improves nanoparticles' hydrophilicity, and trehalose enhances the nanoparticle's cellular internalization by inducing a more auspicious microenvironment based on inhibiting cell surface receptor denaturation. To optimize the nanoprecipitation process, a central composite design was performed; nanoparticles were adsorbed with PEG and trehalose. PLGA nanoparticles with diameters smaller than 200 nm were produced, and the coating process did not considerably increase their size. Nanoparticles entrapped curcumin, and their release profile was determined. The nanoparticles presented a curcumin entrapment efficiency of over 40%, and coated nanoparticles reached 60% of curcumin release in two weeks. MTT tests and curcumin fluorescence, with confocal imaging, were used to assess nanoparticle cytotoxicity and cell internalization in SH-SY5Y cells. Free curcumin 80 µM depleted the cell survival to 13% at 72 h. Contrariwise, PEG:Trehalose-coated curcumin-loaded and non-loaded nanoparticles preserved cell survival at 76% and 79% under the same conditions, respectively. Cells incubated with 100 µM curcumin or curcumin nanoparticles for 1 h exhibited 13.4% and 14.84% of curcumin's fluorescence, respectively. Moreover, cells exposed to 100 µM curcumin in PEG:Trehalose-coated nanoparticles for 1 h presented 28% fluorescence. In conclusion, PEG:Trehalose-adsorbed nanoparticles smaller than 200 nm exhibited suitable neural cytotoxicity and increased cell internalization proficiency. [ABSTRACT FROM AUTHOR]

A new method to evaluate the energy consumption and driving range of electric vehicles running on intercity routes is proposed. This method consists of a hybridization of a predictive method and the application of online information during the driving run. The method uses specific algorithms for dynamic conditions based on real driving conditions, adapting the calculation method to the characteristics of the route and the driving style; electric vehicle characteristics are also taken into consideration for the driving range calculation. Real data were obtained from driving tests in a real electric vehicle under specific driving conditions and compared with the results generated by a simulation process specifically developed for the new method run under the same operating conditions as the real tests. The comparison showed very good agreement, higher than 99%. This method can be customized according to the electric vehicle characteristics, the type of route and the driving style; therefore, it shows an improvement in the determination of the real driving range for an electric vehicle since it applies real driving conditions instead of protocol statistical data. [ABSTRACT FROM AUTHOR]

The recovery of kinetic energy (KER) in electric vehicles was analyzed and characterized. Two main systems were studied: the use of regenerative brakes, and the conversion of potential energy. The paper shows that potential energy is a potential source of kinetic energy recovery with higher efficiency than the traditional system of regenerative brakes. The study compared the rate of KER in both cases for a BMWi3 electric vehicle operating under specific driving conditions; the results of the analysis showed that potential energy conversion can recover up to 88.2%, while the maximum efficiency attained with the regenerative brake system was 60.1%. The study concluded that in driving situations with sudden and frequent changes of vehicle speed due to traffic conditions, such as in urban routes, the use of regenerative brakes was shown to be the best option for KER; however, in intercity routes, driving conditions favored the use of potential energy as a priority system for KER. [ABSTRACT FROM AUTHOR]

Diverse neurological symptoms have been reported in patients with SARSCoV-2 disease (COVID-19), including stroke, ataxia, meningitis, encephalitis, and cognitive impairment. These alterations can cause serious sequelae or death and are associated with the entry of SARS-CoV-2 into the Central Nervous System (CNS). This mini-review discusses the main proposed mechanisms by which SARS-CoV-2 interacts with the blood-brain barrier (BBB) and its involvement in the passage of drugs into the CNS. We performed a search in PubMed with the terms "COVID-19" or "SARS-CoV-2" and "blood-brain barrier injury" or "brain injury" from the year 2019 to 2022. We found proposed evidence that SARS-CoV-2 infects neurovascular cells and increases BBB permeability by increasing the expression of matrix metalloproteinase-9 that degrades type IV collagen in the basement membrane and through activating RhoA, which induces restructuring of the cytoskeleton and alters the integrity of the barrier. The breakdown of the BBB triggers a severe inflammatory response, causing the cytokine storm (release of IL-1b, IL-6, TNF-a, etc.) characteristic of the severe phase of COVID-19, which includes the recruitment of macrophages and lymphocytes and the activation of astrocytes and microglia. We conclude that the increased permeability of the BBB would allow the passage of drugs that would not reach the brain in a normal physiological state, thus enhancing certain drugs' beneficial or adverse effects. We hope this article will encourage research on the impact of drugs on patients with COVID-19 and recovered patients with sequelae, focusing mainly on possible dose adjustments and changes in pharmacokinetic parameters. [ABSTRACT FROM AUTHOR]

Lithium is a therapeutic cation used to treat bipolar disorders but also has some important features as an anti-cancer agent. In this review, we provide a general overview of lithium, from its transport into cells, to its innovative administration forms, and based on genomic, transcriptomic, and proteomic data. Lithium formulations such as lithium acetoacetate (LiAcAc), lithium chloride (LiCl), lithium citrate (Li3C6H5O7), and lithium carbonate (Li2CO3) induce apoptosis, autophagy, and inhibition of tumor growth and also participate in the regulation of tumor proliferation, tumor invasion, and metastasis and cell cycle arrest. Moreover, lithium is synergistic with standard cancer therapies, enhancing their anti-tumor effects. In addition, lithium has a neuroprotective role in cancer patients, by improving their quality of life. Interestingly, nano-sized lithium enhances its anti-tumor activities and protects vital organs from the damage caused by lipid peroxidation during tumor development. However, these potential therapeutic activities of lithium depend on various factors, such as the nature and aggressiveness of the tumor, the type of lithium salt, and its form of administration and dosage. Since lithium has been used to treat bipolar disorder, the current study provides an overview of its role in medicine and how this has changed. This review also highlights the importance of this repurposed drug, which appears to have therapeutic cancer potential, and underlines its molecular mechanisms. [ABSTRACT FROM AUTHOR]

Striatal medium‐sized spiny neurons express mRNA and protein of GPR55 receptors that stimulate neurotransmitter release; thus, GPR55 could be sent to nigral striatal projections, where it might modulate GABA release and motor behavior. Here, we study the presence of GPR55 receptors at striato‐nigral terminals, their modulation of GABA release, their signaling pathway, and their effect on motor activity. By double immunohistochemistry, we found the colocation of GPR55 protein and substance P in the dorsal striatum. In slices of the rat substantia nigra, the GPR55 agonists LPI and O‐1602 stimulated [3H]‐GABA release induced by high K+ depolarization in a dose‐dependent manner. The antagonists CID16020046 and cannabidiol prevented agonist stimulation in a dose‐dependent way. The effect of GPR55 on nigral [3H]‐GABA release was prevented by lesion of the striatum with kainic acid, which was accompanied by a decrement of GPR55 protein in nigral synaptosomes, indicating the presynaptic location of receptors. The depletion of internal Ca2+ stores with thapsigargin did not prevent the effect of LPI on [3H]‐GABA release, but the remotion or chelation of external calcium did. Blockade of Gi, Gs, PLC, PKC, or dopamine D1 receptor signaling proteins did not prevent the effect of GPR55 on release. However, the activation of GPR55 stimulated [3H]‐cAMP accumulation and PKA activity. Intranigral unilateral injection of LPI induces contralateral turning. This turning was prevented by CID16020046, cannabidiol, and bicuculline but not by SCH 23390. Our data indicate that presynaptic GPR55 receptors stimulate [3H]‐GABA release at striato‐nigral terminals through [3H]‐cAMP production and stimulate motor behavior. [ABSTRACT FROM AUTHOR]

The presence of lesions in visible areas of skin may cause emotional troubles in patients, including low self‐worth, embarrassment, sorrow, and social isolation. Those alterations may predispose to psychiatric disorders such as anxiety, depression, and even suicidal ideation, severely affecting patients' health state and quality of life (QoL). In this article, we focus on dermatologic patients that present with secondary mental health alterations. Thus, we offer a detailed description of mental disorders observed in patients with acne vulgaris, atopic dermatitis, psoriasis, ichthyosis, vitiligo, and hidradenitis suppurativa. Moreover, we point out the relationship between the severity of the cutaneous symptoms with mental illnesses and QoL decline. Our objective was to highlight the importance of mental health care for patients with skin diseases. The impact of skin alterations on the mental health of dermatological patients should be a central concern. Likewise, the timely identification and treatment of mental disorders are essential for the comprehensive management of these skin diseases. [ABSTRACT FROM AUTHOR]