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Borneol, camphor, and bornyl acetate are highly promising monoterpenoids widely used in medicine, flavor, food, and chemical applications. Bornyl diphosphate (BPP) serves as a common precursor for the biosynthesis of these monoterpenoids. Although bornyl diphosphate synthase (BPPS) that catalyzes the cyclization of geranyl diphosphate (GPP) to BPP has been identified in multiple plants, the enzyme responsible for the hydrolysis of BPP to produce borneol has not been reported. Here, we conducted in vitro and in vivo functional characterization to identify the Nudix hydrolase WvNUDX24 from W. villosa, which specifically catalyzes the hydrolysis of BPP to generate bornyl phosphate (BP), and then BP forms borneol under the action of phosphatase. Subcellular localization experiments indicated that the hydrolysis of BPP likely occurs in the cytoplasm. Furthermore, site-directed mutagenesis experiments revealed that four critical residues (R84, S96, P98, and G99) for the hydrolysis activity of WvNUDX24. Additionally, the functional identification of phosphatidic acid phosphatase (PAP) demonstrated that WvPAP5 and WvPAP10 were able to hydrolyze geranylgeranyl diphosphate (GGPP) and farnesyl diphosphate (FPP) to generate geranylgeranyl phosphate (GGP) and farnesyl phosphate (FP), respectively, but could not hydrolyze BPP, GPP, and neryl diphosphate (NPP) to produce corresponding monophosphate products. These findings highlight the essential role of WvNUDX24 in the first step of BPP hydrolysis to produce borneol and provide genetic elements for the production of BPP-related terpenoids through plant metabolic engineering and synthetic biology.
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Canfanos , Nudix Hidrolases , Proteínas de Plantas , Pirofosfatases , Pirofosfatases/metabolismo , Pirofosfatases/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Canfanos/metabolismo , Brassicaceae/genética , Brassicaceae/enzimologia , Brassicaceae/metabolismo , Fosfatos de Poli-Isoprenil/metabolismoRESUMO
Fructose-1,6-bisphosphate (FBP), a cellular endogenous sugar metabolite in the glycolytic pathway, has recently been reported to act as a signaling molecule to regulate various cellular events through the engagement of important proteins. Though tremendous progress has been made in identifying specific FBP-protein interactions, the comprehensive identification of FBP-interacting proteins and their regulatory mechanisms remains largely unexplored. Here, we describe a concise synthetic approach for the scalable preparation of a photoaffinity FBP probe that enables the quantitative chemoproteomic profiling of FBP-protein interactions based on photoaffinity labeling (PAL) directly in living cells. Using such a protocol, we captured known FBP targets including PKM2 and MDH2. Furthermore, among unknown FBP-interacting proteins, we identified a mitochondrial metabolic enzyme aldehyde dehydrogenase 2 (ALDH2), against which FBP showed inhibitory activity and resulted in cellular ROS upregulation accompanied by mitochondrial fragmentation. Our findings disclosed a new mode of glucose signaling mediating by the FBP-ALDH2-ROS axis.
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Aldeído-Desidrogenase Mitocondrial , Frutosedifosfatos , Proteômica , Humanos , Frutosedifosfatos/metabolismo , Aldeído-Desidrogenase Mitocondrial/metabolismo , Transdução de Sinais , Espécies Reativas de Oxigênio/metabolismo , Mitocôndrias/metabolismoRESUMO
An efficient, practical, and metal-free protocol for the synthesis of silicon-containing isoindolin-1-ones and deuterated analogues via the synergistic combination of an organic photoredox and hydrogen atom transfer process is described. This strategy features mild reaction conditions, high atom economy, and excellent functional group compatibility, delivering a myriad of structurally diverse and valuable products with good to excellent yields.
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A facile synthetic method for direct C(sp2)-H bond trifluoromethylation of 3-methylene-isoindolin-1-ones under visible-light-induced metal-free conditions is presented. This protocol features mild reaction conditions, broad substrate scope and excellent functional group tolerance, resulting in a range of structurally diverse trifluoromethylated products in good to excellent yields.
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Frizzled receptors (FZDs) are key contributors intrinsic to the Wnt signaling pathway, activation of FZDs triggering the Wnt signaling cascade is frequently observed in human tumors and intimately associated with an aggressive carcinoma phenotype. It has been shown that the abnormal expression of FZD receptors contributes to the manifestation of malignant characteristics in human tumors such as enhanced cell proliferation, metastasis, chemotherapy resistance as well as the acquisition of cancer stemness. Given the essential roles of FZD receptors in the Wnt signaling in human tumors, this review aims to consolidate the prevailing knowledge on the specific status of FZD receptors (FZD1-10) and elucidate their respective functions in tumor progression. Furthermore, we delineate the structural basis for binding of FZD and its co-receptors to Wnt, and provide a better theoretical foundation for subsequent studies on related mechanisms. Finally, we describe the existing biological classes of small molecule-based FZD inhibitors in detail in the hope that they can provide useful assistance for design and development of novel drug candidates targeted FZDs.
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Antineoplásicos , Receptores Frizzled , Neoplasias , Via de Sinalização Wnt , Humanos , Receptores Frizzled/metabolismo , Receptores Frizzled/antagonistas & inibidores , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Via de Sinalização Wnt/efeitos dos fármacos , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , Animais , Terapia de Alvo Molecular/métodosRESUMO
BACKGROUND: The purpose of this research was to stratify the level of frailty to examine the risk factors associated with reversible cognitive frailty (RCF) and potentially reversible cognitive frailty (PRCF) in nursing homes to provide a basis for hierarchical management in different stages of frailty. METHODS: The study was a cross-sectional study conducted from September to November 2022; 504 people were selected by stratified random sampling after convenience selection from the Home for the Aged Guangzhou. The structured questionnaire survey was conducted through face-to-face interviews using the general data questionnaire, Fried Frailty Phenotype, Montreal Cognitive Assessment Scale. RESULTS: In total, 452 individuals were included for analysis. A total of 229 cases (50.7%) were PRCF, 70 (15.5%) were RCF. Multivariate logistic regression analysis showed that in pre-frailty, the Geriatric Depression Scale (GDS-15) score (odds ratio (OR) 1.802; 95% CI 1.308-2.483), Instrumental Activities of Daily Living Scale (IADL) score (0.352; 0.135-0.918) and energy (0.288; 0.110-0.755) were influencing factors of RCF. GDS-15 score (1.805; 1.320-2.468), IADL score (0.268; 0.105-0.682), energy (0.377; 0.150-0.947), lack of intellectual activity (6.118; 1.067-35.070), admission time(>3 years) (9.969; 1.893-52.495) and low education (3.465; 1.211-9.912) were influencing factors of PRCF. However, RCF with frailty was associated with the Short-Form Mini-Nutritional Assessment (MNA-SF) score (0.301; 0.123-0.739) and low education time (0 ~ 12 years) (0.021; 0.001-0.826). PRCF with frailty was associated with age (1.327; 1.081-1.629) and weekly exercise time (0.987; 0.979-0.995). CONCLUSIONS: The prevalence of RCF and PRCF was high among pre-frail and frail older adults in nursing homes. Different levels of frailty had different influencing factors for RCF and PRCF. Depression, daily living ability, energy, intellectual activity, admission time, education level, nutrition status, age and exercise time were associated with RCF and PRCF. Hierarchical management and intervention should be implemented for different stages of frailty to prevent or delay the progression of cognitive frailty.
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Atividades Cotidianas , Disfunção Cognitiva , Idoso Fragilizado , Fragilidade , Avaliação Geriátrica , Instituição de Longa Permanência para Idosos , Casas de Saúde , Humanos , Casas de Saúde/estatística & dados numéricos , Masculino , Feminino , Idoso , Idoso Fragilizado/estatística & dados numéricos , Idoso Fragilizado/psicologia , Estudos Transversais , Fatores de Risco , Prevalência , Avaliação Geriátrica/métodos , Fragilidade/epidemiologia , Fragilidade/psicologia , Idoso de 80 Anos ou mais , Disfunção Cognitiva/epidemiologia , China/epidemiologia , Instituição de Longa Permanência para Idosos/estatística & dados numéricos , Inquéritos e QuestionáriosRESUMO
A left ventricular assist device is a mechanical device that is surgically implanted in the heart to partially or completely replace the function of the heart. Left ventricular assist devices are of vital importance in the treatment of patients with heart failure. There are different recommendations for the postoperative care of patients undergoing left ventricular assist device implantation in different countries, and no uniform standard has been developed. The first implantation of a left ventricular assist device in Eastern China was performed in February 2021; since that date, 14 patients underwent implantation until February 2023. This report describes the postoperative care of these 14 patients with end-stage heart failure who underwent left ventricular assist device placement, all of whom were discharged with a good prognosis.
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Insuficiência Cardíaca , Coração Auxiliar , Humanos , Cuidados Pós-Operatórios , Resultado do Tratamento , Insuficiência Cardíaca/cirurgia , Ventrículos do Coração , China , Coração Auxiliar/efeitos adversos , Estudos RetrospectivosRESUMO
The aim of the present study was to evaluate the diagnostic and prognostic significance of the long non-coding RNA (lncRNA) endoplasmic reticulum membrane protein complex subunit 3 antisense RNA 1 (EMC3-AS1) in liver cancer, and its impact on the proliferative and invasive capabilities of liver cancer cells. EMC3-AS1 expression in liver cancer was assessed using data from The Cancer Genome Atlas and three Gene Expression Omnibus datasets, and validated in clinical liver cancer samples using reverse transcription-quantitative PCR. The prognostic and diagnostic potentials of this lncRNA were evaluated using Kaplan-Meier and receiver operating characteristic analyses, respectively. The infiltration of immune cells and differential expression of immune checkpoints (ICs) between high- and low-EMC3-AS1 expression groups were investigated. Therapeutic correlation analyses were also undertaken to assess the impact of EMC3-AS1 in the treatment of liver cancer. In addition, in vitro experiments were conducted using small interfering RNA to knock down the expression of EMC3-AS1 in HepG2, Sk-Hep-1 and Huh-7 cells, and evaluate the effect on cell proliferation, colony formation and migration. The results revealed a significant upregulation of EMC3-AS1 expression in liver cancer tissues compared with that in adjacent normal tissues, which was associated with an unfavorable prognosis and demonstrated diagnostic effectiveness for patients with liver cancer. Furthermore, patients with high EMC3-AS1 expression exhibited increased levels of IC markers in comparison with those with low EMC3-AS1 expression. In addition, EMC3-AS1 was indicated to have clinical significance in the prediction of the response to immunotherapy and chemotherapy. Notably, the in vitro experiments demonstrated that the knockdown of EMC3-AS1 significantly hindered cell proliferation, colony formation and migration. Consequently, it was concluded that EMC3-AS1 is upregulated in liver cancer and serves as a prognostic indicator for unfavorable outcomes in patients with liver cancer. Additionally, targeting EMC3-AS1 through knockdown interventions showed potential in mitigating the ability of liver cancer cells to proliferate and migrate, which highlights its dual role as a biomarker and therapeutic target for liver cancer.
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The PHB2 gene is located on chromosome 12p13 and encodes prohibitin 2, a highly conserved protein of 37 kDa. PHB2 is a dimer with antiparallel coils, possessing a unique negatively charged region crucial for its mitochondrial molecular chaperone functions. Thus, PHB2 plays a significant role in cell life activities such as mitosis, mitochondrial autophagy, signal transduction, and cell death. This review discusses how PHB2 inhibits transcription factors or nuclear receptors to maintain normal cell functions; how PHB2 in the cytoplasm or membrane ensures normal cell mitosis and regulates cell differentiation; how PHB2 affects mitochondrial structure, function, and cell apoptosis through mitochondrial intimal integrity and mitochondrial autophagy; how PHB2 affects mitochondrial stress and inhibits cell apoptosis by regulating cytochrome c migration and other pathways; how PHB2 affects cell growth, proliferation, and metastasis through a mitochondrial independent mechanism; and how PHB2 could be applied in disease treatment. We provide a theoretical basis and an innovative perspective for a comprehensive understanding of the role and mechanism of PHB2 in cell function regulation.
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Mitocôndrias , Proibitinas , Diferenciação Celular/fisiologia , Proliferação de Células , Mitocôndrias/metabolismo , Transdução de Sinais/fisiologia , HumanosRESUMO
Folliculin interacting protein 1 (FNIP1), a novel folliculin interacting protein 1, is a key regulatory factor for mitochondrial function. FNIP1 mainly responds to energy signal transduction through physical interactions with 5'-AMP activated protein kinase (AMPK). Simultaneously, it affects the transcription of mitochondria-associated genes by regulating the lysosomal localization of mechanistic target of rapamycin kinase (mTORC1). This article takes FNIP1 as the core and first introduces its involvement in the development of B cells and invariant natural killer T (iNKT) cells, muscle fiber type conversion, and the thermogenic remodeling of adipocytes by regulating mitochondrial function. In addition we discuss the detailed impact of upstream regulatory factors of FNIP1 on its function. Finally, the impact of FNIP1 on the prognosis and treatment of clinically related metabolic diseases is summarized, aiming to provide a new theoretical basis and treatment plans for the diagnosis and treatment of such diseases.
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Mitocôndrias , Humanos , Mitocôndrias/metabolismo , Animais , Proteínas de Transporte/metabolismo , Transdução de Sinais , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Doenças Metabólicas/metabolismoRESUMO
Human activities have long impacted the health of Earth's rivers and lakes. These inland waters, crucial for our survival and productivity, have suffered from contamination which allows the formation and spread of antibiotic-resistant genes (ARGs) and consequently, ARG-carrying pathogens (APs). Yet, our global understanding of waterborne pathogen antibiotic resistance remains in its infancy. To shed light on this, our study examined 1240 metagenomic samples from both open and closed inland waters. We identified 22 types of ARGs, 19 types of mobile genetic elements (MGEs), and 14 types of virulence factors (VFs). Our findings showed that open waters have a higher average abundance and richness of ARGs, MGEs, and VFs, with more robust co-occurrence network compared to closed waters. Out of the samples studied, 321 APs were detected, representing a 43 % detection rate. Of these, the resistance gene 'bacA' was the most predominant. Notably, AP hotspots were identified in regions including East Asia, India, Western Europe, the eastern United States, and Brazil. Our research underscores how human activities profoundly influence the diversity and spread of resistome. It also emphasizes that both abiotic and biotic factors play pivotal roles in the emergence of ARG-carrying pathogens.
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Antibacterianos , Genes Bacterianos , Humanos , Resistência Microbiana a Medicamentos/genética , Antibacterianos/farmacologia , Metagenômica , MetagenomaRESUMO
[This corrects the article DOI: 10.1039/D3MD00752A.].
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Soil organic carbon (SOC) is a crucial medium of the global carbon cycle and is profoundly affected by multiple factors, such as climate and management practices. However, interactions between different SOC fractions and land-use change have remained largely unexplored in karst ecosystems with widespread rock outcrops. Owing to the inherent heterogeneity and divergent response of SOC to land-use change, soil samples with close depth were collected from four typical land-use types (cropland, grassland, shrubland, and forestland) in the karst rocky desertification area of China. The aim of this study was to explore the responses of SOC dynamics to land-use types and underlying mechanism. The results showed that land-use type significantly affected SOC contents and its fractions. Compared with cropland, the other three land uses increased the total organic carbon (TOC), microbial biomass carbon (MBC), and non-labile organic carbon (NLOC) contents by 6.11-129.44%, 32.58-173.73%, and 90.98-347.00%, respectively; this demonstrated that a decrease in both labile and recalcitrant carbon resulted in SOC depletion under agricultural land use. Readily oxidized organic carbon (ROC) ranged from 42 to 69%, accounting for almost half of the TOC in the 0-40-cm soil layer. Cropland soil showed significantly higher ROC:TOC ratios than other land-use types. These results indicated that long-term vegetation restoration decreased SOC activity and improved SOC stability. Greater levels of soil exchangeable calcium (ECa) and clay contents were likely responsible for higher stabilization and then accumulation of SOC after vegetation restoration. The carbon pool index (CPI) rather than the carbon pool management index (CPMI) exhibited consistent variation trend with soil TOC contents among land-use types. Thus, further study is needed to validate the CPMI in evaluating land use effects on soil quality in karst ecosystems. Our findings suggest that land-use patterns characterized by grass or forest could be an effective approach for SOC-sequestration potential and ensure the sustainable use of soil resources in the karst area.
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Cálcio , Carbono , Argila , Solo , China , Solo/química , Carbono/análise , Cálcio/análise , Argila/química , Ecossistema , Agricultura , Ciclo do CarbonoRESUMO
Tetrabromobisphenol A (TBBPA) has become a topic of public attention due to its pervasive detection in the environment and organisms in recent decades. However, limited information is available regarding the toxicity of TBBPA on reproductive ability of male mammals. Herein, the reproductive toxicity of TBBPA was investigated in male rats to fill the knowledge gap. In this study, male rats were exposed to TBBPA (0, 10, 100, and 1000â¯mg/kg) for 6 weeks. Subsequently, body and organ indexes, histopathological evaluation of testis and epididymis, ultrastructural observation of sperm, testosterone and progesterone levels, and oxidative stress indicators were conducted to reveal corresponding mechanisms. Results obtained showed that compare to the control group, the body weight, testes weight, epididymis weight, seminal vesicle and coagulation glands weight of rats in the 1000â¯mg/kg group lost 8.30%, 16.84%, 20.16%, 19.72% and 26.42%, respectively. Intriguingly, exposure to TBBPA (10, 100, 100â¯mg/kg) resulted in substantial pathological damage in testis, epididymis and sperm. TBBPA exposure also increased malondialdehyde (MDA) and hydrogen peroxide (H2O2) contents, as well as superoxide dismutase (T-SOD) and catalase (CAT) activities in testicular tissue. What's more, the testosterone and progesterone levels in male rat serum were significantly decreased after exposure to TBBPA for 6 weeks. Meanwhile, results of molecular docking showed that TBBPA has a strong affinity with estrogen receptors (ERs). These findings demonstrated that TBBPA exposure negatively impacts the reproductive ability of male rats, thus providing new insights for risk assessment for reproductive health under TBBPA exposure.
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Disruptores Endócrinos , Estresse Oxidativo , Bifenil Polibromatos , Progesterona , Testículo , Testosterona , Animais , Masculino , Bifenil Polibromatos/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Testículo/efeitos dos fármacos , Testículo/patologia , Testículo/metabolismo , Ratos , Disruptores Endócrinos/toxicidade , Testosterona/sangue , Progesterona/sangue , Espermatozoides/efeitos dos fármacos , Espermatozoides/patologia , Epididimo/efeitos dos fármacos , Epididimo/patologia , Epididimo/metabolismo , Ratos Sprague-Dawley , Tamanho do Órgão/efeitos dos fármacos , Reprodução/efeitos dos fármacos , Simulação de Acoplamento Molecular , Relação Dose-Resposta a DrogaRESUMO
Cytochrome P450 (CYP) enzymes are crucial for the detoxification of xenobiotics, cellular metabolism, and homeostasis. This study investigated the molecular characterization of CYP enzymes in the black-spotted frog, Pelophylax nigromaculatus, and examined the regulation of CYP expression in response to chronic exposure to the antibiotic sulfamethoxazole (SMX) at various environmental concentrations (0, 1, 10, and 100 µg/L). The full-length cDNA of Pn-CYP26B1 was identified. The sequence included open reading frames of 1,536 bp, encoding proteins comprising 511 amino acids. The signature motif, FxxGxxxCxG, was highly conserved when compared with a number of selected animal species. SMX significantly upregulated the expression of the protein CYP26B1 in frog livers at concentrations of 1 and 10 µg/L. SMX showed an affinity for CYP26B1 of -7.6 kcal/mol, indicating a potential mechanism for SMX detoxification or adaptation of the frog. These findings contributed to our understanding of the environmental impact of antibiotics on amphibian species and underscored the importance of CYP enzymes in maintaining biochemical homeostasis under exposure to xenobiotic stress.
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G-quadruplex (G4) aptamers that can competitively binding protein with oncogene promoter G4 hold promise for cancer treatment. In this study, a neutral cytidinyl lipid, DNCA, was shown to transfect and deliver G4 aptamers (AS1411, TBA) into tumour cells, including multidrug-resistant tumour cells, and their nuclear localizations were clearly detected. Both AS1411/DNCA and TBA/DNCA showed excellent antitumour efficacies in the drug-resistant non-small cell lung cancer cell line A549/TXL at a low concentration (100 nM). Heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) was identified as a new target of AS1411 and TBA. The binding affinities were measured, and the Kd values of AS1411/hnRNP A1 and TBA/hnRNP A1 were 17.5 nM and 21.1 nM, respectively. Then the expression of KRAS mRNA in A549/TXL cells was found to be higher than that in A549 cells, and KRAS mRNA was reduced by approximately 40% after administration of AS1411 or TBA in A549/TXL cells. Further, it was confirmed for the first time that AS1411 targeted not only hnRNP A1 but also the KRAS promoter/hnRNP A1 complexes. And although TBA cannot target the KRAS promoter/hnRNP A1 complexes, the biolayer interferometry (BLI) experiment showed that TBA and AS1411 have similar effects on several key proteins in tumour cells, especially hnRNP A1. Molecular docking and molecular dynamics simulation showed that AS1411 and the KRAS promoter bound to the same domain of hnRNP A1 protein, while TBA bound to another domain.
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[This corrects the article DOI: 10.3389/fphar.2017.00476.].
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Collaboration has an essential role in memory, and how to appropriately use it to affect individual memory positively is a matter of concern. The meta-analysis generally assessed the effect of collaboration on subsequent individual retrieval, registered on the PROSPERO platform and adhering to the PRISMA guidelines, using the Web of Science, Science Direct, CNKI and WanFang databases with post-collaborative memory as the main subject, screened studies published up to December 31, 2023, a total of 64 studies with 101 effect sizes, including 13,398 participants from 11 countries. Heterogeneity test, sensitivity analysis, subgroup analysis and meta-regression analysis were performed on the included studies, while publication bias was assessed. The results found that collaboration improves subsequent individual retrieval memory more than individuals, and collaboration has a moderate facilitating effect on subsequent individual retrieval. Group size, material category, category size, collaboration phase, collaboration approach, task process and test method were among the moderating variables. The study emphasizes the role of collaboration in cognition and demonstrates the post-collaborative benefits. The conclusions are of value for developing methods to improve individual memory.
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A supramolecular fluorescence probe has been developed using a symmetrical tetramethyl cucurbit[6]uril (TMeQ[6]) and a styryl derivative (SPy) with a host-guest ratio of 2:1. The introduction of paraquat (PQ) competes with SPy for the TMeQ[6] cavity, resulting in fluorescent quenching. The addition of 17 common herbicides and ions had negligible effects on the fluorescence quenching, indicating that the 2TMeQ[6]/SPy complex exhibits excellent selectivity in detecting PQ. The detection limit was found to be 4.62 × 10-7 M. More importantly, the probe was engineered to detect paraquat in river water by examining post-treatment samples and noting alterations in fluorescence color. The red to blue (R/B) intensity ratio is subsequently calculated to ascertain the PQ concentration. Experimental trials conducted on river water samples yielded recovery rates between 98.21 % and 108 %, with a relative standard deviation of less than 5 %. By pairing this with a smartphone-based colorimetric analysis application, we can facilitate portable PQ detection, enabling efficient and convenient monitoring across various locations.
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Stroke is the most devastating disease, causing paralysis and eventually death. Many clinical and experimental trials have been done in search of a new safe and efficient medicine; nevertheless, scientists have yet to discover successful remedies that are also free of adverse effects. This is owing to the variability in intensity, localization, medication routes, and each patient's immune system reaction. HIF-1α represents the modern tool employed to treat stroke diseases due to its functions: downstream genes such as glucose metabolism, angiogenesis, erythropoiesis, and cell survival. Its role can be achieved via two downstream EPO and VEGF strongly related to apoptosis and antioxidant processes. Recently, scientists paid more attention to drugs dealing with the HIF-1 pathway. This review focuses on medicines used for ischemia treatment and their potential HIF-1α pathways. Furthermore, we discussed the interaction between HIF-1α and other biological pathways such as oxidative stress; however, a spotlight has been focused on certain potential signalling contributed to the HIF-1α pathway. HIF-1α is an essential regulator of oxygen balance within cells which affects and controls the expression of thousands of genes related to sustaining homeostasis as oxygen levels fluctuate. HIF-1α's role in ischemic stroke strongly depends on the duration and severity of brain damage after onset. HIF-1α remains difficult to investigate, particularly in ischemic stroke, due to alterations in the acute and chronic phases of the disease, as well as discrepancies between the penumbra and ischemic core. This review emphasizes these contrasts and analyzes the future of this intriguing and demanding field.