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1.
J Med Chem ; 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38722184

RESUMO

Interleukin-1 receptor-associated kinase 4 (IRAK4) is a promising therapeutic target in inflammation-related diseases. However, the inhibition of IRAK4 kinase activity may lead to moderate anti-inflammatory efficacy owing to the dual role of IRAK4 as an active kinase and a scaffolding protein. Herein, we report the design, synthesis, and biological evaluation of an efficient and selective IRAK4 proteolysis-targeting chimeric molecule that eliminates IRAK4 scaffolding functions. The most potent compound, LC-MI-3, effectively degraded cellular IRAK4, with a half-maximal degradation concentration of 47.3 nM. LC-MI-3 effectively inhibited the activation of downstream nuclear factor-κB signaling and exerted more potent pharmacological effects than traditional kinase inhibitors. Furthermore, LC-MI-3 exerted significant therapeutic effects in lipopolysaccharide- and Escherichia coli-induced acute and chronic inflammatory skin models compared with kinase inhibitors in vivo. Therefore, LC-MI-3 is a candidate IRAK4 degrader in alternative targeting strategies and advanced drug development.

2.
Foods ; 13(9)2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38731692

RESUMO

Previous meta-analyses of multiple studies have suggested that dietary intake and blood concentrations of carotenoids, as well as dietary supplement of certain carotenoids, play a role in reducing the risk of cancer. However, the conclusions of these studies have been subject to controversy. We conducted an umbrella review of meta-analyses to comprehensively analyze and evaluate the evidence pertaining the association between carotenoids and cancer outcomes. We searched PubMed, Web of Science, Embase, and Cochrane Library databases of meta-analyses and systematic reviews up to June 2023. Our selection criteria encompassed meta-analyses of cohort and case-control studies, as well as randomized controlled clinical trials, which investigated the associations between carotenoids and cancer risk. We also determined the levels of evidence for these associations with AMSTAR 2 criteria. We included 51 eligible articles, including 198 meta-analyses for qualitative synthesis in the umbrella review. Despite the presence of moderate to high heterogeneity among the studies, dietary intake, supplementation, and blood concentrations of carotenoids were inversely associated with the risk of total cancer, and certain specific cancers of lung, digestive system, prostate, breast, head and neck, and others. Subgroup analysis also showed that individual carotenoids (α-carotene, ß-carotene, ß-cryptoxanthin, lutein, zeaxanthin, and lycopene) offer certain protection against specific types of cancers. However, high doses of carotenoid supplements, especially ß-carotene, significantly increased the risk of total cancer, lung cancer, and bladder cancer. Our umbrella meta-analysis supported that high intake of dietary carotenoids as a whole food approach could be more beneficial in reducing cancer risk. Concurrently, the findings suggest that the efficacy of single-carotenoid supplementation in cancer prevention remains a subject of controversy.

3.
Water Res ; 257: 121746, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38733966

RESUMO

Sewage sludge is promising for the recovery and utilisation of nutrient components, but its complex nature hinders the release of these components. The combination of pH and thermal modifications shows promise for the release of nutrient components from sludge. However, comprehensive studies on the full spectrum of pH levels and corresponding mechanisms of pH-varying thermal modification are lacking. In this study, the main nutrient components, physicochemical properties, molecular structure, and noncovalent interactions of sludge were comprehensively investigated through pH-varying thermal modification (within a pH range of 2.0 to 12.0 under the same thermal condition). The experimental results showed that the release of main organics, particularly nitrogen (N)-containing organics, was well-fitted, with a tick-like function (R2: 0.74-0.96). The thermal protons exhibited a notable accumulative mutagenic effect on the N-containing organics release, while the thermal hydroxyl ions had a more direct effect, as revealed by the changes in multivalent metals and molecular structures with the protonation-deprotonation of carboxyl groups. The driving force for the release of N-containing organics was identified as the fluctuation of electrostatic interactions at the solid-liquid interface of the sludge. However, the release of phosphorus (P)-containing substances exhibited a contrasting response to that of N-containing substances with varying pH, likely because the reaction sites of thermal protons and thermal hydroxyl ions for P-containing substances were different. Moreover, high concentrations of thermal protons and hydroxyl ions collapsed the Lifshitz-van der Waals interactions of sludge, resulting in a decrease in viscoelasticity and binding strength. These propositions were further confirmed through statistical analyses of the main indicators of the main nutrient components, physicochemical properties, and noncovalent interactions of sludge. These findings can provide a basis for optimising characteristic-specific methods to recovery nutrient components (N/P) from sludge.

4.
Acta Pharmacol Sin ; 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38740904

RESUMO

The circadian clock is the inner rhythm of life activities and is controlled by a self-sustained and endogenous molecular clock, which maintains a ~ 24 h internal oscillation. As the core element of the circadian clock, BMAL1 is susceptible to degradation through the ubiquitin-proteasome system (UPS). Nevertheless, scant information is available regarding the UPS enzymes that intricately modulate both the stability and transcriptional activity of BMAL1, affecting the cellular circadian rhythm. In this work, we identify and validate UBR5 as a new E3 ubiquitin ligase that interacts with BMAL1 by using affinity purification, mass spectrometry, and biochemical experiments. UBR5 overexpression induced BMAL1 ubiquitination, leading to diminished stability and reduced protein level of BMAL1, thereby attenuating its transcriptional activity. Consistent with this, UBR5 knockdown increases the BMAL1 protein. Domain mapping discloses that the C-terminus of BMAL1 interacts with the N-terminal domains of UBR5. Similarly, cell-line-based experiments discover that HYD, the UBR5 homolog in Drosophila, could interact with and downregulate CYCLE, the BMAL1 homolog in Drosophila. PER2-luciferase bioluminescence real-time reporting assay in a mammalian cell line and behavioral experiments in Drosophila reveal that UBR5 or hyd knockdown significantly reduces the period of the circadian clock. Therefore, our work discovers a new ubiquitin ligase UBR5 that regulates BMAL1 stability and circadian rhythm and elucidates the underlying molecular mechanism. This work provides an additional layer of complexity to the regulatory network of the circadian clock at the post-translational modification, offering potential insights into the modulation of the dysregulated circadian rhythm.

5.
Nat Neurosci ; 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38741020

RESUMO

The subcommissural organ (SCO) is a gland located at the entrance of the aqueduct of Sylvius in the brain. It exists in species as distantly related as amphioxus and humans, but its function is largely unknown. Here, to explore its function, we compared transcriptomes of SCO and non-SCO brain regions and found three genes, Sspo, Car3 and Spdef, that are highly expressed in the SCO. Mouse strains expressing Cre recombinase from endogenous promoter/enhancer elements of these genes were used to genetically ablate SCO cells during embryonic development, resulting in severe hydrocephalus and defects in neuronal migration and development of neuronal axons and dendrites. Unbiased peptidomic analysis revealed enrichment of three SCO-derived peptides, namely, thymosin beta 4, thymosin beta 10 and NP24, and their reintroduction into SCO-ablated brain ventricles substantially rescued developmental defects. Together, these data identify a critical role for the SCO in brain development.

6.
Bioresour Technol ; : 130856, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38763204

RESUMO

The inductive effect of conductive materials (CMs) on enhancing methanogenesis metabolism has been overlooked. Herein, we highlight role of CMs in inducing the spatial optimisation of methanogenic consortia by altering the Lewis acid-base (AB) interactions within microbial aggregates. In the presence of CMs and after their removal, the methane production and methane proportion in biogas significantly increase, with no significant difference between the two situations. Analyses of interactions between CMs and extracellular polymer substances (EPSs) with and without D2O reveal that CMs promote release and transfer potential of electron in EPSs, which induce and enhance the role of water molecules being primarily as proton acceptors in the hydrogen bonding between EPSs and water, thereby changing the electron-donor- and electron-acceptor-based AB interactions. Investigations of succession dynamics of microbial communities, co-occurrence networks, and metagenomics further indicate that electron transfer drives the microbial spatial optimisation for efficient methanogenesis through intensive interspecies interactions.

7.
PLoS One ; 19(5): e0302742, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38768144

RESUMO

Zeaxanthin dipalmitate (ZD) is a chemical extracted from wolfberry that protects degenerated photoreceptors in mouse retina. However, the pure ZD is expensive and hard to produce. In this study, we developed a method to enrich ZD from wolfberry on a production line and examined whether it may also protect the degenerated mouse retina. The ZD-enriched wolfberry extract (ZDE) was extracted from wolfberry by organic solvent method, and the concentration of ZD was identified by HPLC. The adult C57BL/6 mice were treated with ZDE or solvent by daily gavage for 2 weeks, at the end of the first week the animals were intraperitoneally injected with N-methyl-N-nitrosourea to induce photoreceptor degeneration. Then optomotor, electroretinogram, and immunostaining were used to test the visual behavior, retinal light responses, and structure. The final ZDE product contained ~30mg/g ZD, which was over 9 times higher than that from the dry fruit of wolfberry. Feeding degenerated mice with ZDE significantly improved the survival of photoreceptors, enhanced the retinal light responses and the visual acuity. Therefore, our ZDE product successfully alleviated retinal morphological and functional degeneration in mouse retina, which may provide a basis for further animal studies for possible applying ZDE as a supplement to treat degenerated photoreceptor in the clinic.


Assuntos
Modelos Animais de Doenças , Lycium , Camundongos Endogâmicos C57BL , Células Fotorreceptoras de Vertebrados , Extratos Vegetais , Degeneração Retiniana , Zeaxantinas , Animais , Lycium/química , Degeneração Retiniana/tratamento farmacológico , Degeneração Retiniana/patologia , Camundongos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Zeaxantinas/farmacologia , Células Fotorreceptoras de Vertebrados/efeitos dos fármacos , Células Fotorreceptoras de Vertebrados/patologia , Eletrorretinografia , Retina/efeitos dos fármacos , Retina/patologia , Retina/metabolismo , Visão Ocular/efeitos dos fármacos , Masculino , Xantofilas/farmacologia
8.
Microsyst Nanoeng ; 10: 62, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38770032

RESUMO

This study elaborates on the design, fabrication, and data analysis details of SPEED, a recently proposed smartphone-based digital polymerase chain reaction (dPCR) device. The dPCR chips incorporate partition diameters ranging from 50 µm to 5 µm, and these partitions are organized into six distinct blocks to facilitate image processing. Due to the superior thermal conductivity of Si and its potential for mass production, the dPCR chips were fabricated on a Si substrate. A temperature control system based on a high-power density Peltier element and a preheating/cooling PCR protocol user interface shortening the thermal cycle time. The optical design employs four 470 nm light-emitting diodes as light sources, with filters and mirrors effectively managing the light emitted during PCR. An algorithm is utilized for image processing and illumination nonuniformity correction including conversion to a monochromatic format, partition identification, skew correction, and the generation of an image correction mask. We validated the device using a range of deoxyribonucleic acid targets, demonstrating its potential applicability across multiple fields. Therefore, we provide guidance and verification of the design and testing of the recently proposed SPEED device.

9.
Cell Metab ; 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38772364

RESUMO

Circadian disruption predicts poor cancer prognosis, yet how circadian disruption is sensed in sleep-deficiency (SD)-enhanced tumorigenesis remains obscure. Here, we show fatty acid oxidation (FAO) as a circadian sensor relaying from clock disruption to oncogenic metabolic signal in SD-enhanced lung tumorigenesis. Both unbiased transcriptomic and metabolomic analyses reveal that FAO senses SD-induced circadian disruption, as illustrated by continuously increased palmitoyl-coenzyme A (PA-CoA) catalyzed by long-chain fatty acyl-CoA synthetase 1 (ACSL1). Mechanistically, SD-dysregulated CLOCK hypertransactivates ACSL1 to produce PA-CoA, which facilitates CLOCK-Cys194 S-palmitoylation in a ZDHHC5-dependent manner. This positive transcription-palmitoylation feedback loop prevents ubiquitin-proteasomal degradation of CLOCK, causing FAO-sensed circadian disruption to maintain SD-enhanced cancer stemness. Intriguingly, timed ß-endorphin resets rhythmic Clock and Acsl1 expression to alleviate SD-enhanced tumorigenesis. Sleep quality and serum ß-endorphin are negatively associated with both cancer development and CLOCK/ACSL1 expression in patients with cancer, suggesting dawn-supplemented ß-endorphin as a potential chronotherapeutic strategy for SD-related cancer.

10.
Paediatr Anaesth ; 2024 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-38736282

RESUMO

In China, healthcare has lagged relative to its economic boom during the past 40 years. While the top tier hospitals offer pediatric perioperative care like high-income countries, lower-tier hospitals deliver lesser services of variable quality and safety related to equipment, supplies, clinician education, and availability. The national residency training program and the pediatric anesthesia fellowship program was established in 2013 and 2018 respectively. Increasing clinician workload from patient demand and a lack of consistency in quality and capability between rural and urban areas remain challenging.

11.
Braz J Med Biol Res ; 57: e13474, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38716985

RESUMO

Coenzyme Q10 (CoQ10) is a potent antioxidant that is implicated in the inhibition of osteoclastogenesis, but the underlying mechanism has not been determined. We explored the underlying molecular mechanisms involved in this process. RAW264.7 cells received receptor activator of NF-κB ligand (RANKL) and CoQ10, after which the differentiation and viability of osteoclasts were assessed. After the cells were treated with CoQ10 and/or H2O2 and RANKL, the levels of reactive oxygen species (ROS) and proteins involved in the PI3K/AKT/mTOR and MAPK pathways and autophagy were tested. Moreover, after the cells were pretreated with or without inhibitors of the two pathways or with the mitophagy agonist, the levels of autophagy-related proteins and osteoclast markers were measured. CoQ10 significantly decreased the number of TRAP-positive cells and the level of ROS but had no significant impact on cell viability. The relative phosphorylation levels of PI3K, AKT, mTOR, ERK, and p38 were significantly reduced, but the levels of FOXO3/LC3/Beclin1 were significantly augmented. Moreover, the levels of FOXO3/LC3/Beclin1 were significantly increased by the inhibitors and mitophagy agonist, while the levels of osteoclast markers showed the opposite results. Our data showed that CoQ10 prevented RANKL-induced osteoclastogenesis by promoting autophagy via inactivation of the PI3K/AKT/mTOR and MAPK pathways in RAW264.7 cells.


Assuntos
Autofagia , Osteoclastos , Osteogênese , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Ligante RANK , Serina-Treonina Quinases TOR , Ubiquinona , Animais , Camundongos , Autofagia/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/fisiologia , Osteoclastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ligante RANK/metabolismo , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Ubiquinona/análogos & derivados , Ubiquinona/farmacologia
12.
Sci Rep ; 14(1): 11572, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773298

RESUMO

Down-polyethylene film material has been introduced for the first time as an excellent non-frame sound absorber, showing a distinctively outstanding performance. It contains down fiber adjacent to each other without firm connection in between, forming a structure of elastic fiber network. The unique structure has broadband response to sound wave, showing non-synchronous vibration in low and middle frequency and synchronous vibration in middle and high frequency. The broadband resonance in middle and high frequency allows the structure to achieve complete sound absorption in resonance frequency band. Moreover, down-polyethylene film material possesses forced vibration, corresponding sound absorption coefficient has been obtained based on vibration theory. The down-film sound absorption material has the characteristics of light weight, soft, environment-friendly, and has excellent broadband sound absorption performance.

13.
Heliyon ; 10(9): e30640, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38774102

RESUMO

The skeletal muscle is the largest organ in mammals and is the primary motor function organ of the body. Our previous research has shown that long non-coding RNAs (lncRNAs) are significant in the epigenetic control of skeletal muscle development. Here, we observed progressive upregulation of lncRNA 4930581F22Rik expression during skeletal muscle differentiation. Knockdown of lncRNA 4930581F22Rik hindered skeletal muscle differentiation and resulted in the inhibition of the myogenic markers MyHC and MEF2C. Furthermore, we found that lncRNA 4930581F22Rik regulates myogenesis via the ERK/MAPK signaling pathway, and this effect could be attenuated by the ERK-specific inhibitor PD0325901. Additionally, in vivo mice injury model results revealed that lncRNA 4930581F22Rik is involved in skeletal muscle regeneration. These results establish a theoretical basis for understanding the contribution of lncRNAs in skeletal muscle development and regeneration.

14.
Mol Neurobiol ; 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38775879

RESUMO

Autophagy is an intracellular recycling process that maintains cellular homeostasis by degrading excess or defective macromolecules and organelles. Chaperone-mediated autophagy (CMA) is a highly selective form of autophagy in which a substrate containing a KFERQ-like motif is recognized by a chaperone protein, delivered to the lysosomal membrane, and then translocated to the lysosome for degradation with the assistance of lysosomal membrane protein 2A. Normal CMA activity is involved in the regulation of cellular proteostasis, metabolism, differentiation, and survival. CMA dysfunction disturbs cellular homeostasis and directly participates in the pathogenesis of human diseases. Previous investigations on CMA in the central nervous system have primarily focus on neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease. Recently, mounting evidence suggested that brain injuries involve a wider range of types and severities, making the involvement of CMA in the bidirectional processes of damage and repair even more crucial. In this review, we summarize the basic processes of CMA and its associated regulatory mechanisms and highlight the critical role of CMA in brain injury such as cerebral ischemia, traumatic brain injury, and other specific brain injuries. We also discuss the potential of CMA as a therapeutic target to treat brain injury and provide valuable insights into clinical strategies.

15.
J Phys Chem Lett ; : 5594-5599, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38755539

RESUMO

In recent years, silver nanoparticles (Ag NPs) have been used as positive electrode material for zinc/silver batteries, and the silver oxides formed during the charging process determine the discharge performance of batteries. Therefore, it is important to study the oxidation behavior of Ag NPs in alkaline solution. Single-nanoparticle collision is an important tool for analyzing oxidation behavior of individual nanoparticles. Based on thermodynamic information from collision events, it is known that oxidation products are potential-dependent and size-dependent. Based on dynamic information, including collisional peak shapes and duration time, it was observed that the Ag NP collision oxidation process changed from stepwise oxidation to direct oxidation as the potential increased or size decreased. This work provides guidance for application of Ag NPs in zinc/silver batteries and proposed a strategy for oxidation behavior of individual NP that could be tracked in situ through an all-encompassing view of thermodynamic and dynamic information.

16.
Endocrine ; 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38758293

RESUMO

PURPOSE: The current study investigated the correlation between dietary iron intake and diabetic kidney disease among diabetic adults. METHODS: This cross-sectional study enrolled 8118 participants who suffered from diabetes from the National Health and Nutrition Examination Survey (NHANES) 1999-2018. Dietary iron intake was obtained from 24 h recall interviews, and diabetic kidney disease was defined as eGFR < 60 mL/min per 1.73 m2 or albumin creatinine ratio (ACR) ≥ 30 mg/g. Three weighted logistic regression models were utilized to investigate odd ratio (OR) and 95% CIs for diabetic kidney disease. Stratified analyses were performed by gender, age, BMI, HbA1c, hypertension status, and smoking status, and diabetes types. RESULTS: Among 8118 participants (51.6% male, mean age 61.3 years), 40.7% of participants suffered from diabetic kidney disease. With the adjustment of potential covariates, we found that ≥ 12.59 mg of dietary iron was related to a lower risk of diabetic kidney disease (OR = 0.78, 95% CI: 0.63 to 0.96; OR = 0.79, 95% CI: 0.63 to 0.98). In stratified analyses, higher iron intake was negatively related to diabetic kidney disease, especially among those who were male, < 60 years, those with hypertension, those with HbA1c < 7.0%, and those who were ex-smokers. The result remained robust in sensitivity analyses. CONCLUSION: We found that ≥ 12.59 mg of dietary iron is associated with a lower risk of diabetic kidney disease, especially in those who were male, younger, heavier weight, have better blood sugar control, and those who were ex-smokers.

17.
Int J Biol Macromol ; 270(Pt 1): 132258, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38735613

RESUMO

Covalently linking an adjuvant to an antigenic protein enhances its immunogenicity by ensuring a synergistic delivery to the immune system, fostering a more robust and targeted immune response. Most adjuvant-protein conjugate vaccines incorporate only one adjuvant due to the difficulties in its synthesis. However, there is a growing interest in developing vaccines with multiple adjuvants designed to elicit a more robust and targeted immune response by engaging different aspects of the immune system for complex diseases where traditional vaccines fall short. Here, we pioneer the synthesis of a dual-adjuvants protein conjugate Vaccine 1 by assembling a toll-like receptor 7/8 (TLR7/8) agonist, an invariant natural killer T cell (iNKT) agonist with a clickable bicyclononyne (BCN). The BCN group can bio-orthogonally react with azide-modified severe acute respiratory syndrome coronavirus-2 receptor-binding domain (SARS-CoV-2 RBD) trimer antigen to give the three-component Vaccine 1. Notably, with a mere 3 µg antigen, it elicited a balanced subclass of IgG titers and 20-fold more IgG2a than control vaccines, highlighting its potential for enhancing antibody-dependent cellular cytotoxicity. This strategy provides a practicable way to synthesize covalently linked dual immunostimulants. It expands the fully synthetic self-adjuvant protein vaccine that uses a single adjuvant to include two different types of adjuvants.

18.
Sci Total Environ ; 931: 172887, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38692317

RESUMO

Solar interface evaporation is an effective method for the treatment of water that has low energy consumption. Adsorption is recognized to be one of the most stable wastewater treatment methods and is widely used. Combining solar interface evaporation with adsorption provides a novel and low-cost approach for the efficient removal of heavy metals and organic pollutants from industrial wastewater. This paper reviews the characteristics and application of some common wastewater treatment methods. The photothermal conversion and the conceptual design of interface evaporation combined with adsorption are introduced and the photo-thermal conversion and adsorption methods are discussed. The study provides a summary of recent studies and advancements in interfacial evaporation-coupled adsorption materials, which include hydrogels, aerogels, and biomass materials for adsorption, and carbon materials for photothermal conversion. Finally, the current challenges encountered in industrial wastewater treatment are outlined and its prospects are discussed. The aim of this review is to explore a wide range of possibilities with the interfacial evaporation-coupled adsorption method and propose a new low-cost and high-efficiency method for industrial wastewater treatment.

19.
Phytomedicine ; 129: 155681, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38718638

RESUMO

BACKGROUND: Infertility patients account for an astonishing proportion of individuals worldwide. Due to its complex etiology and challenging treatment, infertility has imposed significant psychological and economic burdens on many patients. C. Herba (Cistanche tubulosa (Schenk) Wight and Cistanche deserticola Ma), renowned as one of the most prominent Chinese herbal medicines (CHMs), is abundant in diverse bioactive compounds that exhibit therapeutic effects on many diseases related to oxidative stress (OS) and disorders of sex hormone levels. OBJECTIVE: Due to the limited drugs currently used in clinical practice to improve reproductive outcomes and their inevitable side effects, developing safe and effective new medications for infertility is of significance. This article comprehensively reviewed the phytochemicals of C. Herba, focusing on their efficacy and mechanisms on infertility and their safety for the first time, aiming to offer valuable insights for the development and application of C. Herba, and for developing novel strategies for treating infertility. METHODS: We used "Cistanche" and its known bioactive components in combination with "sperm", "testicles", "epididymis", "ovaries", "uterus", and "infertility" as keywords to search in PubMed, Web of Science, Scopus and CNKI up to November 2023. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guideline was followed. RESULTS: The therapeutic effects of C. Herba on infertility are mainly attributed to echinacoside (ECH), verbascoside (VB), salidroside (SAL), polysaccharides, and betaine. They can effectively improve spermatogenic dysfunction, gonadal dysfunction and erectile dysfunction (ED) by exerting anti-oxidation, sex hormones regulation and anti-hypoxia. Moreover, they can also improve premature ovarian failure (POF), ovarian and uterine cancer, oocyte maturation by exerting anti-oxidation, anti-apoptosis, and anti-cancer. C. Herba and its active ingredients also exhibit pleasing safety. CONCLUSION: C. Herba is a promising source of natural medicine for infertility. Additionally, compared to current therapeutic drugs, its favorable safety also supports its development as a nutritional supplement. However, high-quality clinical studies are required to validate its effectiveness for the development of novel therapeutic strategies.

20.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 40(4): 311-318, 2024 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-38710515

RESUMO

Objective To investigate the effects of mitochondrial transcription factor A (TFAM) on mitochondrial function, autophagy, proliferation, invasion, and migration in cervical cancer HeLa cells and osteosarcoma U2OS cells. Methods TFAM small-interfering RNA (si-TFAM) was transfected to HeLa and U2OS cells for downregulating TFAM expression. Mito-Tracker Red CMXRos staining combined with laser confocal microscopy was used to detect mitochondrial membrane potential (MMP). MitoSOXTM Red labeling was used to test mitochondrial reactive oxygen species (mtROS) levels. The expression of mitochondrial DNA (mtDNA) was detected by real-time quantitative PCR. Changes in the number of autophagosomes were detected by immunofluorescence cytochemistry. Western blot analysis was used to detect the expressions of TFAM, autophagy microtubule associated protein 1 light chain 3A/B (LC3A/B), autophagy associated protein 2A (ATG2A), ATG2B, ATG9A, zinc finger transcription factor Snail, matrix metalloproteinase 2 (MMP2) and MMP9. CCK-8 assay and plate clony formation assay were used to detect cell proliferation, while TranswellTM assay and scratch healing assay were used to detect changes in cell invasion and migration. Results The downregulation of TFAM expression resulted in a decrease in MMP and mtDNA copy number, but an increase in mtROS production. The protein content of LC3A/B decreased significantly compared to the control group and the number of autophagosomes in the cytoplasm decreased significantly. The expressions of ATG2B and ATG9A in the early stage of autophagy were significantly reduced. The expressions of Snail, MMP2 and MMP9 proteins in HeLa and U2OS cells were also decreased. The proliferation, invasion and migration ability of HeLa and U2OS cells were inhibited after being interfered with TFAM expression. Conclusion Downregulation of TFAM expression inhibits mitochondrial function, delays autophagy process and reduces the proliferation, invasion and migration ability of cervical cancer cells and osteosarcoma cells.


Assuntos
Autofagia , Movimento Celular , Proliferação de Células , Proteínas de Ligação a DNA , Proteínas Mitocondriais , Invasividade Neoplásica , Osteossarcoma , Fatores de Transcrição , Neoplasias do Colo do Útero , Humanos , Movimento Celular/genética , Osteossarcoma/genética , Osteossarcoma/patologia , Osteossarcoma/metabolismo , Proliferação de Células/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Autofagia/genética , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Feminino , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/metabolismo , Linhagem Celular Tumoral , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Potencial da Membrana Mitocondrial/genética , Espécies Reativas de Oxigênio/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 2 da Matriz/genética , Mitocôndrias/metabolismo , Mitocôndrias/genética , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , Células HeLa , Metaloproteinase 9 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética
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