Seven Colletotrichum acutatum strains isolated from strawberries were cultivated on various culture media and tested in vitro and in vivo on Fragaria x ananassa for anthracnose symptoms. PDA caused an optimum growth o...Seven Colletotrichum acutatum strains isolated from strawberries were cultivated on various culture media and tested in vitro and in vivo on Fragaria x ananassa for anthracnose symptoms. PDA caused an optimum growth of all isolates, MEA, ML and Strawberry allowed a good but not optimal growth. Czapeck, Sabouraud and the organic medium from potato gave the lowest growth rate of all isolates. PDA allowed a good sporulation of isolates follow-up by strawberry, MEA;in contrast, ML, Czapeck and Sabouraud gave a low sporulation. The fungal development is maximal at 25°C and 27°C for all the isolates studied. No growth was observed at 5°C and 37°C. The studied strains developed at all pH values. They didn’t develop at 0.6, 0.65 and 0.7 aw but mycelial growth was perfect at 1 and 0.95 aw. The in vitro test of the pathogenicity caused by C. acutatum strains on strawberry’s leaves showed an increasing percentage of infection with time and different infection rates among C. acutatum strains, strain Ca6 having a pathogenic power very high compared to the other isolates. After in vivo inoculation and incubation of the seedlings, all isolates caused severe symptoms related to anthracnose on leaflets and petioles of the studied strawberry plants.展开更多
Genetic,epigenetic,and metabolic alterations are all hallmarks of cancer.However,the epigenome and metabolome are both highly complex and dynamic biological networks in vivo.The interplay between the epigenome and met...Genetic,epigenetic,and metabolic alterations are all hallmarks of cancer.However,the epigenome and metabolome are both highly complex and dynamic biological networks in vivo.The interplay between the epigenome and metabolome contributes to a biological system that is responsive to the tumor microenvironment and possesses a wealth of unknown biomarkers and targets of cancer therapy.From this perspective,we first review the state of high-throughput biological data acquisition(i.e.multiomics data)and analysis(i.e.computational tools)and then propose a conceptual in silico metabolic and epigenetic regulatory network(MER-Net)that is based on these current high-throughput methods.The conceptual MER-Net is aimed at linking metabolomic and epigenomic networks through observation of biological processes,omics data acquisition,analysis of network information,and integration with validated database knowledge.Thus,MER-Net could be used to reveal new potential biomarkers and therapeutic targets using deep learning models to integrate and analyze large multiomics networks.We propose that MER-Net can serve as a tool to guide integrated metabolomics and epigenomics research or can be modified to answer other complex biological and clinical questions using multiomics data.展开更多
Amyotrophic lateral sclerosis is the most common adult-onset neurodegenerative disease affecting motor neurons. Its defining feature is progressive loss of motor neuron function in the cortex, brainstem, and spinal co...Amyotrophic lateral sclerosis is the most common adult-onset neurodegenerative disease affecting motor neurons. Its defining feature is progressive loss of motor neuron function in the cortex, brainstem, and spinal cord, leading to paralysis and death. Despite major advances in identifying genes that can cause disease when mutated and model the disease in animals and cellular models, it still remains unclear why motor symptoms suddenly appear after a long pre-symptomatic phase of apparently normal function. One hypothesis is that age-related deregulation of specific proteins within key cell types, especially motor neurons themselves, initiates disease symptom appearance and may also drive progressive degeneration. Genome-wide in vivo cell-type-specific screening tools are enabling identification of candidates for such proteins. In this minireview, we first briefly discuss the methodology used in a recent study that applied a motor neuron-specific RNASeq screening approach to a standard model of TAR DNA-binding protein-43(TDP-43)-driven amyotrophic lateral sclerosis. A key finding of this study is that synaptogyrin-4 and pleckstrin homology domain-containing family B member 1 are also deregulated at the protein level within motor neurons of two unrelated mouse models of mutant TDP-43 driven amyotrophic lateral sclerosis. Guided by what is known about molecular and cellular functions of these proteins and their orthologs, we outline here specific hypotheses for how changes in their levels might potentially alter cellular physiology of motor neurons and detrimentally affect motor neuron function. Where possible, we also discuss how this information could potentially be used in a translational context to develop new therapeutic strategies for this currently incurable, devastating disease.展开更多
The valorization of crop residues could constitute an energy source (biogas) allowing to reduce the energy needs of populations in agricultural regions, improve their living conditions and slow down deforestation as w...The valorization of crop residues could constitute an energy source (biogas) allowing to reduce the energy needs of populations in agricultural regions, improve their living conditions and slow down deforestation as well as greenhouse gas emissions. This work aims to determine the typology of agricultural waste in the departments of Soubré, Sassandra, Daloa and Issia, to determine the number of residues generated in these departments, and to assess the biogas potential of these departments said residues. Field observations were made to identify the different types of waste, then, based on agricultural statistical data from the Ministry of Agriculture and biogas productivity indexes, the quantities of agricultural residues and biogas were estimated. Agricultural residues consist of pods (50%), stalks (19%), cobs (3%), Straws (8%), stalks (2%), shells (9%), fibers (7%), husks (1%), and bunches (1%). In addition, these localities have 465266.3 t of pods, 173583.2 t of stalks, 84280.0 t of shells, 75,857 t of straws, 12,000 t of husks, 10,987 t of bunches and 6793.0 t of fibers. The departments of Soubré, Sassandra, Daloa and Issia contain a total potential energy of 235.87 × 10<sup>6</sup> m<sup>3</sup> of biogas. However, this is unevenly distributed among the localities. The volume of biogas recorded is higher in the department of Soubré (74.91 × 10<sup>6</sup> m<sup>3</sup>) which is followed respectively by the departments of Daloa (62.27 × 10<sup>6</sup> m<sup>3</sup>), Issia (52.77 × 10<sup>6</sup> m<sup>3</sup> and Sassandra (45.93 × 10<sup>6</sup> m<sup>3</sup>). The departments of Soubré, Sassandra, Daloa and Issia have a very large potential for the production of agricultural residues that may be of interest to economic operators for recovery in biogas production units.展开更多
Stress signaling following axon injury stimulates a transcriptional program for regeneration that might be exploited to promote central nervous system repair.However,this stress response drives neuronal apoptosis in n...Stress signaling following axon injury stimulates a transcriptional program for regeneration that might be exploited to promote central nervous system repair.However,this stress response drives neuronal apoptosis in non-regenerative environments.This duality presents a quandary for the development of therapeutic interventions:manipulating stress signaling to enhance recovery of damaged neurons risks accelerating neurodegeneration or restricting regenerative potential.This dichotomy is well illustrated by the fates of retinal ganglion cells(RGCs)following optic nerve crush.In this central nervous system injury model,disruption of a stress-activated MAP kinase(MAPK)cascade blocks the extensive apoptosis of RGCs that occurs in wild-type mice(Watkins et al.,2013;Welsbie et al.,2017).展开更多
This study investigates the critical issue of radiation contamination in Mailuu-Suu,Kyrgyzstan,a legacy of extensive uranium mining and milling operations during the Soviet era.The research centers on the environmenta...This study investigates the critical issue of radiation contamination in Mailuu-Suu,Kyrgyzstan,a legacy of extensive uranium mining and milling operations during the Soviet era.The research centers on the environmental behavior and health impacts of radon-222 and associated radionuclides emanating from uranium mill tailings.A comprehensive year-long indoor radon monitoring program(July 2001-July 2002)revealed radon concentrations that substantially exceeded the national Radiation Safety Standards(RSS-96),posing serious health risks to local populations.Approximately 1.9 million cubic meters of uranium mill tailings,distributed across multiple unsecured waste dumps,were assessed for their radiological burden.While precise activity levels remain undocumented,it is estimated that these tailings represent tens of thousands of tonnes of radioactive material.Based on typical uranium ore residue densities and grades,this volume could contain over 3-5 million tonnes of material,with estimated activities ranging from 10^(13) to 10^(15) becquerels,depending on radionuclide composition.Epidemiological data indicate elevated rates of cancer,respiratory illnesses,and congenital anomalies,particularly among vulnerable groups such as children,pregnant women,and the elderly.The findings highlight an urgent need for targeted environmental remediation,continuous radiological surveillance,and public health strategies to mitigate long-term risks and enhance ecological and human safety in the region.展开更多
Abstract:In today’s economy,determining accessible and affordable techniques to remove Heavy Metals(HMs)from wastewater is crucial.Activated carbon is highly effective in adsorbing HMs due to its large surface area a...Abstract:In today’s economy,determining accessible and affordable techniques to remove Heavy Metals(HMs)from wastewater is crucial.Activated carbon is highly effective in adsorbing HMs due to its large surface area and porous structure.It works by attracting and binding HM ions to its surface.Okoubaka is known for its medicinal properties and some studies suggest it has detoxifying effects.However,its specific role in HM removal would likely involve binding mechanisms like other plant-based materials.This study examines the efficiency of activated charcoal,charred versus uncharred Okoubaka plant materials,eggshells and oxalic acid to remove HMs like copper,lead,and zinc from contaminated water.展开更多
Objective:To investigate the effects of quercetin on inflammatory signaling pathways and hepatic oxidative injury using a streptozotocin-induced liver injury model.Methods:Four groups of 32 rats were used in this stud...Objective:To investigate the effects of quercetin on inflammatory signaling pathways and hepatic oxidative injury using a streptozotocin-induced liver injury model.Methods:Four groups of 32 rats were used in this study:three groups were given streptozotocin to induce diabetes,and one group was given a normal control.For treatment groups,each group received either metformin(200 mg/kg body weight)or quercetin(50 mg/kg body weight)for a month.The expression of SREBP1c was detected by quantitative RT-PCR and fibrosis-related proteins(TGF-βand p-Smad3)was evaluated by Western blot.Furthermore,MCP and IL-1βwere determined by ELISA.Results:Quercetin significantly reduced insulin and glucose levels.Besides,it reduced the serum levels of ALT,AST,and ALP,improved lipid profile,lowered the MDA level,increased SOD activity,decreased the rise in MCP-1 and IL-1β,inhibited the TGF-β/Smad3 signaling pathway,decreasedα-SMA and SREBP1c expression,and increased AMPK(P<0.05).Conclusions:Quercetin could significantly mitigate hepatic damage by modulating the expression of pro-inflammatory cytokines and fibrosis markers.展开更多
This study demonstrates the valorization of macadamia nutshells,a lignocellulosic agricultural waste,as both a carbon source for amylase production and a support matrix for enzyme immobilization.Under optimized solid-...This study demonstrates the valorization of macadamia nutshells,a lignocellulosic agricultural waste,as both a carbon source for amylase production and a support matrix for enzyme immobilization.Under optimized solid-state fermentation conditions,Aspergillus niger ICP2 synthesized amylase with a peak activity of 0.312 U/mL after 72 hours.A four-step purification process of the crude enzyme extract resulted in a 188.54-fold increase in specific activity,albeit with a final recovery yield of 0.0031%.In parallel,nutshells were carbonized at 600℃,700℃,and 800℃,then chemically activated with ZnCl_(2).The carbon derived at 700℃ exhibited superior physicochemical characteristics,including enhanced porosity and increased availability of functional groups,which enabled effective enzyme adsorption,improved catalytic performance,and enhanced reusability.Immobilized amylase on this support retained approximately 30% of its initial activity after five hydrolysis cycles,demonstrating moderate operational reusability and potential for repeated use in bioprocesses.In contrast,carbon materials from 600℃ and 800℃ showed lower stability and enzyme performance.These findings highlight the critical role of carbonization conditions in designing effective immobilization matrices and underscore the potential of macadamia nutshells as a renewable and sustainable resource for biocatalyst development.This“biowaste-to-biocatalyst”strategy exemplifies a circular bioeconomy model with implications for green chemistry,industrial biocatalysis,and environmental sustainability.展开更多
The rising risk of synthetic preservatives as antimicrobial agent has increased,leading to potential allergic reactions,intoxications,cancer,and other degenerative diseases.As a result,essential oils(EOs),recognized a...The rising risk of synthetic preservatives as antimicrobial agent has increased,leading to potential allergic reactions,intoxications,cancer,and other degenerative diseases.As a result,essential oils(EOs),recognized as natural antimicrobial agents due to their extensive antibacterial properties,have gained attention.However,their industrial applicability is hindered by challenges such as volatility,poor water solubility,oxidation potential,photodegradation,and thermal instability.Nano-encapsulation has emerged as a transformative solution for delivering essential oils,enhancing their stability,bioavailability,and targeted administration.This review explores the use of nano-encapsulated essential oils in combating bacteria,focusing on their mechanisms of action and potential advancements for the food preservation industry.Various nano-encapsulation methods,including liposomes,nanoemulsions,polymeric nanoparticles,and biopolymers like chitosan and alginate,have shown promise in overcoming the limitations associated with EOs.展开更多
Background:Plants are known to produce a diverse group of natural metabolites with different biological activities.Centaurea ensiformis P.H.Davis,Origanum hypericifolium O.Schwartz&P.H.Davis,and Paeonia turcica Da...Background:Plants are known to produce a diverse group of natural metabolites with different biological activities.Centaurea ensiformis P.H.Davis,Origanum hypericifolium O.Schwartz&P.H.Davis,and Paeonia turcica Davis&Cullen are endemic plant species that grow on mountains in select regions in Türkiye and have been used in traditional Turkish medicine for various ailments.Methods:As first,we evaluated the larvicidal and antibiofilm activities of ethanol,ethyl acetate,acetone,and water extracts obtained from these plants.Antioxidant activities of the extracts were also investigated.Results:All tested extracts were effective at concentrations>25 ppm on Aedes aegypti larval mortality with the lethal concentration 50(LC_(50))values ranging between 32.82-48.35 ppm and LC90 between 46.26-63.2 ppm.O.hypericifolium was the most effective plant,ethanol extracts presented LC50 values of 32.82 ppm.Extracts demonstrated varying degrees of antibiofilm activity depending on the dose and bacterial species.Origanum hypericifolium extracts notably inhibited biofilms of Staphylococcus aureus(up to 98%inhibition),while P.turcica showed moderate efficacy against the same bacterial species.Pseudomonas aeruginosa biofilms displayed high resistance to all extracts.Conclusion:The results indicated that these endemic Turkish plants possess promising larvicidal and antibiofilm potential,particularly Origanum hypericifolium.Extracts analyzed by liquid chromatography-tandem mass spectrometry contained caffeic acid,myricetin,cinnamic acid,quercetin,gallic acid,epicatechin,and ascorbic acid.Further research should explore their potential applications in mosquito control and biofilm-related infections.展开更多
Cultural ecosystem services(CES)provided by urban green infrastructure are essential for enhancing social well-being and resilience.Identifying and mapping CES at a local scale is crucial for informed land-use decisio...Cultural ecosystem services(CES)provided by urban green infrastructure are essential for enhancing social well-being and resilience.Identifying and mapping CES at a local scale is crucial for informed land-use decisions that align with citizens'perceptions.However,research on ecosystem services in Romania has been limited,with a notable gap in the assessment of CES provided by urban green spaces.This study is the first to focus on Băneasa Forest,the only urban forest in Bucharest,which serves as a vital recreational area for thousands of residents and visitors.For the first time in Romania,this research uses a web-based Participatory GIS survey to collect spatially referenced data.The survey,which combines questionnaires and mapping exercises,allows us to produce high-resolution CES maps based on 816 responses.The results reveal that the forest's natural characteristics are perceived as the primary contributors to CES.These findings are valuable for urban planners,as they highlight the needs and expectations of forest visitors,promote conservation efforts,and foster collaboration to prevent conflicts.Alongside factors frequently discussed in the literature,such as age and accessibility,the percentage of green space in residents'neighborhoods emerges as a significant factor influencing CES preferences.This insight presents a novel contribution to the literature,being of particular importance for urban planners and policymakers,as it underscores the need to consider not just the green space within parks and forests,but also the broader context of surrounding neighborhoods when planning for CES.Understanding that the availability of nearby green space influences residents'CES preferences can guide more effective strategies to enhance access to CES in urban areas,both in Bucharest and elsewhere.This is especially relevant in the face of climate change and other emerging challenges,which are likely to increase the demand for CES in the future.展开更多
The general objective of our study was to describe the clinical and epidemiological aspects of anxiety disorders. This was a retrospective descriptive cross-sectional study, lasting 5 years, from January 01, 2019 to D...The general objective of our study was to describe the clinical and epidemiological aspects of anxiety disorders. This was a retrospective descriptive cross-sectional study, lasting 5 years, from January 01, 2019 to December 31, 2023, on 225 patients seen in consultation for anxiety disorders in the department. The prevalence of anxiety disorders was 2.5% in consultation. The 20 - 29 age group was the most represented at 33.3%. Females were slightly represented at 55.1%, with a sex ratio of 1.2. The secondary level was the most affected, accounting for 36.4% of cases. Insomnia was the most frequent reason for consultation, accounting for 71.1% of cases. A larger general population study would be necessary to better assess the extent of anxiety disorders in Guinea.展开更多
Fifty-four Levantine vipers,Macrovipera lebetinus(Linnaeus,1758)(27♀♀,16♂♂,and 11 juveniles)collected from 14 provinces of Türkiye between April 2007 and May 2020 were examined helminthologically.This is the ...Fifty-four Levantine vipers,Macrovipera lebetinus(Linnaeus,1758)(27♀♀,16♂♂,and 11 juveniles)collected from 14 provinces of Türkiye between April 2007 and May 2020 were examined helminthologically.This is the first helminthological study on M.lebetinus collected in Türkiye.Two species of Cestoda(Mesocestoides sp.,Ophiotaenia europea),5 species of Nematoda(Abbreviata sp.,Ophidascaris excavata,Paracapillaria(Ophidiocapillaria)sp.,Pharyngodon sp.,Strongyloides sp.),and 2 species of Acanthocephala(Sphaerirostris corvi and unidentified cystacanths)were found.These species are considered to be common species of snakes.Paracapillaria(Ophidiocapillaria)sp.represents a record for M.lebetinus.Abbreviata sp.,Mesocestoides sp.,Ophidascaris excavata,Paracapillaria sp.,Pharyngodon sp.,Strongyloides sp.,and Sphaerirostsris corvi represent new records for snakes of Türkiye.展开更多
Objectives:Cisplatin(CDDP)therapy for glioblastoma(GBM)is linked with several limitations,which include poor penetration of the blood-brain barrier(BBB),systemic toxicity,and the development of drug resistance mechani...Objectives:Cisplatin(CDDP)therapy for glioblastoma(GBM)is linked with several limitations,which include poor penetration of the blood-brain barrier(BBB),systemic toxicity,and the development of drug resistance mechanisms implicating oxidative stress dysregulation and compromised apoptotic pathways.This study evaluates C-Phycocyanin(C-PC)as a potential adjuvant to enhance CDDP efficacy by modulating redox balance and apoptosis.Methods:GBM cells(U87 and U87-EGFRvIII)were treated with CDDP,C-PC,or their combination.Cell viability was assessed by MTT assay;apoptosis was evaluated by DAPI staining andWestern blot analysis of cleaved Caspase-3 and poly(ADP-ribose)polymerase(PARP).Both intracellular and extracellular reactive oxygen species(ROS)were measured using 2′,7′-dichlorodihydrofluorescein diacetate(DCF-DA)fluorescence and lucigenin chemiluminescence,respectively.Catalase activity was quantified via hydrogen peroxide(H2O2)decomposition assay,and manganese superoxide dismutase(MnSOD)expression byWestern blot.Results:C-PCselectively decreased U87GBMcell viability while sparing normal cells.C-PC enhanced CDDP cytotoxicity,reducing viability to 26.5%vs.53.2%for CDDP alone.This effect correlated with increased apoptosis,evidenced by DNA fragmentation and higher cleaved caspase-3 and PARP levels.Combined treatment lowered ROS below survival thresholds while upregulating MnSOD and catalase activity.In U87-EGFRvIII cells,CDDP reduced viability modestly(85.2%),C-PC alone decreased viability significantly(51.5%)and induced cell death,but the combination did not further increase apoptosis.Here,C-PC’s pro-apoptotic effects,alone or with CDDP,were also associated with reduced oxidative stress in cells.Conclusion:We demonstrate that C-PC enhances CDDP cytotoxicity in sensitive U87 cells by promoting apoptosis and modulating ROS,suggesting potential for improved therapeutic efficacy with reduced systemic toxicity.Compared to the combination,C-PC monotherapy achieves superior cytotoxicity in CDDP-resistant U87-EGFRvIII cells,underscoring its potential as a standalone therapeutic approach for chemotherapy-resistant glioblastoma subtypes.展开更多
Two new free-living marine nematode species belonging to the genus Tricoma Cobb,1894(Desmoscolecidae)are identi-fied from the continental shelf region of the Bay of Bengal.Tricoma ajmalia sp.nov.is characterized by th...Two new free-living marine nematode species belonging to the genus Tricoma Cobb,1894(Desmoscolecidae)are identi-fied from the continental shelf region of the Bay of Bengal.Tricoma ajmalia sp.nov.is characterized by the number of main rings(84 male and 85 female),the arrangement of somatic setae,the head shape with broadly truncated end,the relatively long cephalic setae(69%-73%of corresponding head diameter),the amphids extending up to second main ring,slender spicules slightly curved and gu-berbaculum with dorsocaudally directed apophyses.The second new species,Tricoma sampadansis sp.nov.is characterized by the number of rings(64),the arrangement of somatic setae(14-13 subdorsal,16 subvenral),the head shape with broadly truncated end,the relatively long cephalic setae(75%corresponding head diameter),the amphidial fovea extending over first main ring,anterioirly bent spicules and gubernaculum with hooked proximal end.An updated valid species list of Tricoma is also presented.展开更多
The interest in using the Datura stramonium plant is due to its natural products,which are used in many pharmaceutical industries.The objective of the current study was to assess the therapeutic and cytotoxic effects ...The interest in using the Datura stramonium plant is due to its natural products,which are used in many pharmaceutical industries.The objective of the current study was to assess the therapeutic and cytotoxic effects of the D.stramonium plant on two types of human cancer cell models(MCF7 and HT29)in vitro.A soxhlet apparatus was used to obtain methanolic extract from dried plant leaves.The recovered crude,after the solvent had evaporated,was then dispersed at varied concentrations of extract 100,50,20,and 0.0µg/mL and tested to see how the cells responded.Also,the cancer-testis antigen(CTA)gene transcription in the two cell types exposed to the plant extract was examined using a semi-quantitative real-time polymerase chain reaction.Gas chromatography–mass spectrometry(GC-MS)results produced the significant main metabolites Nonanoic acid,Tropine N-Oxide,3,6-Ditigloyloxy-7-hydroxytropane,Hexadecanoic acid,2-Pentadecanone,6,10,14-trimethyl-,Carvenone,methyl ester,Phytol,Aposcopolamine,Hyoscyamine,4,8,12,16-Tetramethylheptadecan-4-olide,Scopolamine,Alpha.-Tocospiro A,1,2-Cycloheptanedione,3,3,7,7-tetramethyl-,dihydrazone,Campesterol,Stigmasterol,Gamma-Sitosterol and dl-.alpha.-Tocopherol.The results showed that the two types of cell lines impacted by D.stramonium extract,through untreated type 1 cells(MCF7)gave a highly significant transcription according to all applicable genes.All implemented analyses cleared the strong genetic impacts of Datura extract on cancer cells’genomes.TGIF2LY and C2orf63 transcript accumulation were also significantly elevated when exposed to plant extract at a level of 50µg/mL in cell line type 2(HT29),but TGIF2LY and P53 had the lowest relative expression at a level of 100µg/mL when treated the same cell line type.展开更多
Clinical translation of tissue-engineered advanced therapeutic medicinal products is hindered by a lack of patient-dependent and independent in-process biological quality controls that are reflective of in vivo outcom...Clinical translation of tissue-engineered advanced therapeutic medicinal products is hindered by a lack of patient-dependent and independent in-process biological quality controls that are reflective of in vivo outcomes.Recent insights into the mechanism of native bone repair highlight a robust path dependence.Organoid-based bottom-up developmental engineering mimics this pathdependence to design personalized living implants scaffold-free,with in-build outcome predictability.Yet,adequate(noninvasive)quality metrics of engineered tissues are lacking.Moreover,insufficient insight into the role of donor variability and biological sex as influencing factors for the mechanism toward bone repair hinders the implementation of such protocols for personalized bone implants.Here,male and female bone-forming organoids were compared to non-bone-forming organoids regarding their extracellular matrix composition,transcriptome,and secreted proteome signatures to directly link in vivo outcomes to quality metrics.As a result,donor variability in bone-forming callus organoids pointed towards two distinct pathways to bone,through either a hypertrophic cartilage or a fibrocartilaginous template.The followed pathway was determined early,as a biological sexdependent activation of distinct progenitor populations.Independent of donor or biological sex,a cartilage-to-bone transition was driven by a common panel of secreted factors that played a role in extracellular matrix remodeling,mineralization,and attraction of vasculature.Hence,the secreted proteome is a source of noninvasive biomarkers that report on biological potency and could be the missing link toward data-driven decision-making in organoid-based bone tissue engineering.展开更多
Our previous study has demonstrated that procyanidin A_(1)(A_(1))and its simulated digestive product(D-A_(1))can prevent acrylamide(ACR)-induced cytotoxicity in small intestine cells.However,the potential mechanism re...Our previous study has demonstrated that procyanidin A_(1)(A_(1))and its simulated digestive product(D-A_(1))can prevent acrylamide(ACR)-induced cytotoxicity in small intestine cells.However,the potential mechanism remains poorly understood.In this study,ACR treatment was found to increase the levels of 8-hydroxy deoxyguanine(8-OHdG)and phosphorated histone H_(2)AX(γH_(2)AX),two DNA damage markers,thereby resulting in cell cycle arrest in the G2/M phase;whereas both A_(1) and D-A_(1) could prevent the phosphorylation of ataxia telangiectasia mutated(ATM)and checkpoint kinase 2(Chk2),and then regulate the expression of G2/M phase-related proteins,finally maintaining normal cell cycle progression.Moreover,A_(1) and D-A_(1) could increase the B cell lymphoma 2(Bcl-2)/Bcl2-associated X(Bax)ratio and decrease the expression of cleaved caspase-3 and cleaved caspase-9 proteins to alleviate ACR-induced cell apoptosis,which might be related to the inhibition of the mitogen-activated protein kinase(MAPK)pathway.More importantly,A_(1) showed no remarkable variation in inhibitory effect before and after digestion,indicating that it can endure gastrointestinal digestion and may be a promising phytochemical to alleviate ACR-induced intestinal cell damage.展开更多
文摘Seven Colletotrichum acutatum strains isolated from strawberries were cultivated on various culture media and tested in vitro and in vivo on Fragaria x ananassa for anthracnose symptoms. PDA caused an optimum growth of all isolates, MEA, ML and Strawberry allowed a good but not optimal growth. Czapeck, Sabouraud and the organic medium from potato gave the lowest growth rate of all isolates. PDA allowed a good sporulation of isolates follow-up by strawberry, MEA;in contrast, ML, Czapeck and Sabouraud gave a low sporulation. The fungal development is maximal at 25°C and 27°C for all the isolates studied. No growth was observed at 5°C and 37°C. The studied strains developed at all pH values. They didn’t develop at 0.6, 0.65 and 0.7 aw but mycelial growth was perfect at 1 and 0.95 aw. The in vitro test of the pathogenicity caused by C. acutatum strains on strawberry’s leaves showed an increasing percentage of infection with time and different infection rates among C. acutatum strains, strain Ca6 having a pathogenic power very high compared to the other isolates. After in vivo inoculation and incubation of the seedlings, all isolates caused severe symptoms related to anthracnose on leaflets and petioles of the studied strawberry plants.
基金supported by the National Natural Science Foundation of China(81890994,31871343)National Key Research and Development Program of China(2017YFA0505503,2018YFB0704304,2018YFA0801402)+1 种基金the WBE Liver Fibrosis Foundation(CFHPC 2020021)the Beijing Dongcheng District outstanding talent funding project and the Beijing Undergraduate Training Programs for Innovation and Entrepreneurship(202010023046)。
文摘Genetic,epigenetic,and metabolic alterations are all hallmarks of cancer.However,the epigenome and metabolome are both highly complex and dynamic biological networks in vivo.The interplay between the epigenome and metabolome contributes to a biological system that is responsive to the tumor microenvironment and possesses a wealth of unknown biomarkers and targets of cancer therapy.From this perspective,we first review the state of high-throughput biological data acquisition(i.e.multiomics data)and analysis(i.e.computational tools)and then propose a conceptual in silico metabolic and epigenetic regulatory network(MER-Net)that is based on these current high-throughput methods.The conceptual MER-Net is aimed at linking metabolomic and epigenomic networks through observation of biological processes,omics data acquisition,analysis of network information,and integration with validated database knowledge.Thus,MER-Net could be used to reveal new potential biomarkers and therapeutic targets using deep learning models to integrate and analyze large multiomics networks.We propose that MER-Net can serve as a tool to guide integrated metabolomics and epigenomics research or can be modified to answer other complex biological and clinical questions using multiomics data.
基金supported in part by funding from the Else Kr?ner Fresenius Stiftung(Co-PI)the Werner Otto Stiftung(PI)(to KED)。
文摘Amyotrophic lateral sclerosis is the most common adult-onset neurodegenerative disease affecting motor neurons. Its defining feature is progressive loss of motor neuron function in the cortex, brainstem, and spinal cord, leading to paralysis and death. Despite major advances in identifying genes that can cause disease when mutated and model the disease in animals and cellular models, it still remains unclear why motor symptoms suddenly appear after a long pre-symptomatic phase of apparently normal function. One hypothesis is that age-related deregulation of specific proteins within key cell types, especially motor neurons themselves, initiates disease symptom appearance and may also drive progressive degeneration. Genome-wide in vivo cell-type-specific screening tools are enabling identification of candidates for such proteins. In this minireview, we first briefly discuss the methodology used in a recent study that applied a motor neuron-specific RNASeq screening approach to a standard model of TAR DNA-binding protein-43(TDP-43)-driven amyotrophic lateral sclerosis. A key finding of this study is that synaptogyrin-4 and pleckstrin homology domain-containing family B member 1 are also deregulated at the protein level within motor neurons of two unrelated mouse models of mutant TDP-43 driven amyotrophic lateral sclerosis. Guided by what is known about molecular and cellular functions of these proteins and their orthologs, we outline here specific hypotheses for how changes in their levels might potentially alter cellular physiology of motor neurons and detrimentally affect motor neuron function. Where possible, we also discuss how this information could potentially be used in a translational context to develop new therapeutic strategies for this currently incurable, devastating disease.
文摘The valorization of crop residues could constitute an energy source (biogas) allowing to reduce the energy needs of populations in agricultural regions, improve their living conditions and slow down deforestation as well as greenhouse gas emissions. This work aims to determine the typology of agricultural waste in the departments of Soubré, Sassandra, Daloa and Issia, to determine the number of residues generated in these departments, and to assess the biogas potential of these departments said residues. Field observations were made to identify the different types of waste, then, based on agricultural statistical data from the Ministry of Agriculture and biogas productivity indexes, the quantities of agricultural residues and biogas were estimated. Agricultural residues consist of pods (50%), stalks (19%), cobs (3%), Straws (8%), stalks (2%), shells (9%), fibers (7%), husks (1%), and bunches (1%). In addition, these localities have 465266.3 t of pods, 173583.2 t of stalks, 84280.0 t of shells, 75,857 t of straws, 12,000 t of husks, 10,987 t of bunches and 6793.0 t of fibers. The departments of Soubré, Sassandra, Daloa and Issia contain a total potential energy of 235.87 × 10<sup>6</sup> m<sup>3</sup> of biogas. However, this is unevenly distributed among the localities. The volume of biogas recorded is higher in the department of Soubré (74.91 × 10<sup>6</sup> m<sup>3</sup>) which is followed respectively by the departments of Daloa (62.27 × 10<sup>6</sup> m<sup>3</sup>), Issia (52.77 × 10<sup>6</sup> m<sup>3</sup> and Sassandra (45.93 × 10<sup>6</sup> m<sup>3</sup>). The departments of Soubré, Sassandra, Daloa and Issia have a very large potential for the production of agricultural residues that may be of interest to economic operators for recovery in biogas production units.
基金supported by grants from Mission Connect, a project of the TIRR Foundation, the Glaucoma Research FoundationNIH grants R01NS112691 and R01NS076708 (to TAW)
文摘Stress signaling following axon injury stimulates a transcriptional program for regeneration that might be exploited to promote central nervous system repair.However,this stress response drives neuronal apoptosis in non-regenerative environments.This duality presents a quandary for the development of therapeutic interventions:manipulating stress signaling to enhance recovery of damaged neurons risks accelerating neurodegeneration or restricting regenerative potential.This dichotomy is well illustrated by the fates of retinal ganglion cells(RGCs)following optic nerve crush.In this central nervous system injury model,disruption of a stress-activated MAP kinase(MAPK)cascade blocks the extensive apoptosis of RGCs that occurs in wild-type mice(Watkins et al.,2013;Welsbie et al.,2017).
文摘This study investigates the critical issue of radiation contamination in Mailuu-Suu,Kyrgyzstan,a legacy of extensive uranium mining and milling operations during the Soviet era.The research centers on the environmental behavior and health impacts of radon-222 and associated radionuclides emanating from uranium mill tailings.A comprehensive year-long indoor radon monitoring program(July 2001-July 2002)revealed radon concentrations that substantially exceeded the national Radiation Safety Standards(RSS-96),posing serious health risks to local populations.Approximately 1.9 million cubic meters of uranium mill tailings,distributed across multiple unsecured waste dumps,were assessed for their radiological burden.While precise activity levels remain undocumented,it is estimated that these tailings represent tens of thousands of tonnes of radioactive material.Based on typical uranium ore residue densities and grades,this volume could contain over 3-5 million tonnes of material,with estimated activities ranging from 10^(13) to 10^(15) becquerels,depending on radionuclide composition.Epidemiological data indicate elevated rates of cancer,respiratory illnesses,and congenital anomalies,particularly among vulnerable groups such as children,pregnant women,and the elderly.The findings highlight an urgent need for targeted environmental remediation,continuous radiological surveillance,and public health strategies to mitigate long-term risks and enhance ecological and human safety in the region.
基金The Sherman Fairchild Foundation Undergraduate Research GrantThe National Science Foundation Award#1912400:HBCU-UP Implementation Project:Improving Minority Participation and Completion through STEM at Dillard University(IMPACTS@DU Ⅱ)Dillard University Endowed Professorship,funds。
文摘Abstract:In today’s economy,determining accessible and affordable techniques to remove Heavy Metals(HMs)from wastewater is crucial.Activated carbon is highly effective in adsorbing HMs due to its large surface area and porous structure.It works by attracting and binding HM ions to its surface.Okoubaka is known for its medicinal properties and some studies suggest it has detoxifying effects.However,its specific role in HM removal would likely involve binding mechanisms like other plant-based materials.This study examines the efficiency of activated charcoal,charred versus uncharred Okoubaka plant materials,eggshells and oxalic acid to remove HMs like copper,lead,and zinc from contaminated water.
文摘Objective:To investigate the effects of quercetin on inflammatory signaling pathways and hepatic oxidative injury using a streptozotocin-induced liver injury model.Methods:Four groups of 32 rats were used in this study:three groups were given streptozotocin to induce diabetes,and one group was given a normal control.For treatment groups,each group received either metformin(200 mg/kg body weight)or quercetin(50 mg/kg body weight)for a month.The expression of SREBP1c was detected by quantitative RT-PCR and fibrosis-related proteins(TGF-βand p-Smad3)was evaluated by Western blot.Furthermore,MCP and IL-1βwere determined by ELISA.Results:Quercetin significantly reduced insulin and glucose levels.Besides,it reduced the serum levels of ALT,AST,and ALP,improved lipid profile,lowered the MDA level,increased SOD activity,decreased the rise in MCP-1 and IL-1β,inhibited the TGF-β/Smad3 signaling pathway,decreasedα-SMA and SREBP1c expression,and increased AMPK(P<0.05).Conclusions:Quercetin could significantly mitigate hepatic damage by modulating the expression of pro-inflammatory cytokines and fibrosis markers.
基金a funded project under the 2024 Hibah Penelitian Produktivitas Guru Besar(Professor Research Productivity Grant)scheme at Jember University.
文摘This study demonstrates the valorization of macadamia nutshells,a lignocellulosic agricultural waste,as both a carbon source for amylase production and a support matrix for enzyme immobilization.Under optimized solid-state fermentation conditions,Aspergillus niger ICP2 synthesized amylase with a peak activity of 0.312 U/mL after 72 hours.A four-step purification process of the crude enzyme extract resulted in a 188.54-fold increase in specific activity,albeit with a final recovery yield of 0.0031%.In parallel,nutshells were carbonized at 600℃,700℃,and 800℃,then chemically activated with ZnCl_(2).The carbon derived at 700℃ exhibited superior physicochemical characteristics,including enhanced porosity and increased availability of functional groups,which enabled effective enzyme adsorption,improved catalytic performance,and enhanced reusability.Immobilized amylase on this support retained approximately 30% of its initial activity after five hydrolysis cycles,demonstrating moderate operational reusability and potential for repeated use in bioprocesses.In contrast,carbon materials from 600℃ and 800℃ showed lower stability and enzyme performance.These findings highlight the critical role of carbonization conditions in designing effective immobilization matrices and underscore the potential of macadamia nutshells as a renewable and sustainable resource for biocatalyst development.This“biowaste-to-biocatalyst”strategy exemplifies a circular bioeconomy model with implications for green chemistry,industrial biocatalysis,and environmental sustainability.
文摘The rising risk of synthetic preservatives as antimicrobial agent has increased,leading to potential allergic reactions,intoxications,cancer,and other degenerative diseases.As a result,essential oils(EOs),recognized as natural antimicrobial agents due to their extensive antibacterial properties,have gained attention.However,their industrial applicability is hindered by challenges such as volatility,poor water solubility,oxidation potential,photodegradation,and thermal instability.Nano-encapsulation has emerged as a transformative solution for delivering essential oils,enhancing their stability,bioavailability,and targeted administration.This review explores the use of nano-encapsulated essential oils in combating bacteria,focusing on their mechanisms of action and potential advancements for the food preservation industry.Various nano-encapsulation methods,including liposomes,nanoemulsions,polymeric nanoparticles,and biopolymers like chitosan and alginate,have shown promise in overcoming the limitations associated with EOs.
文摘Background:Plants are known to produce a diverse group of natural metabolites with different biological activities.Centaurea ensiformis P.H.Davis,Origanum hypericifolium O.Schwartz&P.H.Davis,and Paeonia turcica Davis&Cullen are endemic plant species that grow on mountains in select regions in Türkiye and have been used in traditional Turkish medicine for various ailments.Methods:As first,we evaluated the larvicidal and antibiofilm activities of ethanol,ethyl acetate,acetone,and water extracts obtained from these plants.Antioxidant activities of the extracts were also investigated.Results:All tested extracts were effective at concentrations>25 ppm on Aedes aegypti larval mortality with the lethal concentration 50(LC_(50))values ranging between 32.82-48.35 ppm and LC90 between 46.26-63.2 ppm.O.hypericifolium was the most effective plant,ethanol extracts presented LC50 values of 32.82 ppm.Extracts demonstrated varying degrees of antibiofilm activity depending on the dose and bacterial species.Origanum hypericifolium extracts notably inhibited biofilms of Staphylococcus aureus(up to 98%inhibition),while P.turcica showed moderate efficacy against the same bacterial species.Pseudomonas aeruginosa biofilms displayed high resistance to all extracts.Conclusion:The results indicated that these endemic Turkish plants possess promising larvicidal and antibiofilm potential,particularly Origanum hypericifolium.Extracts analyzed by liquid chromatography-tandem mass spectrometry contained caffeic acid,myricetin,cinnamic acid,quercetin,gallic acid,epicatechin,and ascorbic acid.Further research should explore their potential applications in mosquito control and biofilm-related infections.
基金supported by the University of Bucharest through the“People and trees”CIVIS project.
文摘Cultural ecosystem services(CES)provided by urban green infrastructure are essential for enhancing social well-being and resilience.Identifying and mapping CES at a local scale is crucial for informed land-use decisions that align with citizens'perceptions.However,research on ecosystem services in Romania has been limited,with a notable gap in the assessment of CES provided by urban green spaces.This study is the first to focus on Băneasa Forest,the only urban forest in Bucharest,which serves as a vital recreational area for thousands of residents and visitors.For the first time in Romania,this research uses a web-based Participatory GIS survey to collect spatially referenced data.The survey,which combines questionnaires and mapping exercises,allows us to produce high-resolution CES maps based on 816 responses.The results reveal that the forest's natural characteristics are perceived as the primary contributors to CES.These findings are valuable for urban planners,as they highlight the needs and expectations of forest visitors,promote conservation efforts,and foster collaboration to prevent conflicts.Alongside factors frequently discussed in the literature,such as age and accessibility,the percentage of green space in residents'neighborhoods emerges as a significant factor influencing CES preferences.This insight presents a novel contribution to the literature,being of particular importance for urban planners and policymakers,as it underscores the need to consider not just the green space within parks and forests,but also the broader context of surrounding neighborhoods when planning for CES.Understanding that the availability of nearby green space influences residents'CES preferences can guide more effective strategies to enhance access to CES in urban areas,both in Bucharest and elsewhere.This is especially relevant in the face of climate change and other emerging challenges,which are likely to increase the demand for CES in the future.
文摘The general objective of our study was to describe the clinical and epidemiological aspects of anxiety disorders. This was a retrospective descriptive cross-sectional study, lasting 5 years, from January 01, 2019 to December 31, 2023, on 225 patients seen in consultation for anxiety disorders in the department. The prevalence of anxiety disorders was 2.5% in consultation. The 20 - 29 age group was the most represented at 33.3%. Females were slightly represented at 55.1%, with a sex ratio of 1.2. The secondary level was the most affected, accounting for 36.4% of cases. Insomnia was the most frequent reason for consultation, accounting for 71.1% of cases. A larger general population study would be necessary to better assess the extent of anxiety disorders in Guinea.
文摘Fifty-four Levantine vipers,Macrovipera lebetinus(Linnaeus,1758)(27♀♀,16♂♂,and 11 juveniles)collected from 14 provinces of Türkiye between April 2007 and May 2020 were examined helminthologically.This is the first helminthological study on M.lebetinus collected in Türkiye.Two species of Cestoda(Mesocestoides sp.,Ophiotaenia europea),5 species of Nematoda(Abbreviata sp.,Ophidascaris excavata,Paracapillaria(Ophidiocapillaria)sp.,Pharyngodon sp.,Strongyloides sp.),and 2 species of Acanthocephala(Sphaerirostris corvi and unidentified cystacanths)were found.These species are considered to be common species of snakes.Paracapillaria(Ophidiocapillaria)sp.represents a record for M.lebetinus.Abbreviata sp.,Mesocestoides sp.,Ophidascaris excavata,Paracapillaria sp.,Pharyngodon sp.,Strongyloides sp.,and Sphaerirostsris corvi represent new records for snakes of Türkiye.
文摘Objectives:Cisplatin(CDDP)therapy for glioblastoma(GBM)is linked with several limitations,which include poor penetration of the blood-brain barrier(BBB),systemic toxicity,and the development of drug resistance mechanisms implicating oxidative stress dysregulation and compromised apoptotic pathways.This study evaluates C-Phycocyanin(C-PC)as a potential adjuvant to enhance CDDP efficacy by modulating redox balance and apoptosis.Methods:GBM cells(U87 and U87-EGFRvIII)were treated with CDDP,C-PC,or their combination.Cell viability was assessed by MTT assay;apoptosis was evaluated by DAPI staining andWestern blot analysis of cleaved Caspase-3 and poly(ADP-ribose)polymerase(PARP).Both intracellular and extracellular reactive oxygen species(ROS)were measured using 2′,7′-dichlorodihydrofluorescein diacetate(DCF-DA)fluorescence and lucigenin chemiluminescence,respectively.Catalase activity was quantified via hydrogen peroxide(H2O2)decomposition assay,and manganese superoxide dismutase(MnSOD)expression byWestern blot.Results:C-PCselectively decreased U87GBMcell viability while sparing normal cells.C-PC enhanced CDDP cytotoxicity,reducing viability to 26.5%vs.53.2%for CDDP alone.This effect correlated with increased apoptosis,evidenced by DNA fragmentation and higher cleaved caspase-3 and PARP levels.Combined treatment lowered ROS below survival thresholds while upregulating MnSOD and catalase activity.In U87-EGFRvIII cells,CDDP reduced viability modestly(85.2%),C-PC alone decreased viability significantly(51.5%)and induced cell death,but the combination did not further increase apoptosis.Here,C-PC’s pro-apoptotic effects,alone or with CDDP,were also associated with reduced oxidative stress in cells.Conclusion:We demonstrate that C-PC enhances CDDP cytotoxicity in sensitive U87 cells by promoting apoptosis and modulating ROS,suggesting potential for improved therapeutic efficacy with reduced systemic toxicity.Compared to the combination,C-PC monotherapy achieves superior cytotoxicity in CDDP-resistant U87-EGFRvIII cells,underscoring its potential as a standalone therapeutic approach for chemotherapy-resistant glioblastoma subtypes.
基金the Centre for Marine Living Resources and Ecology (CMLRE),Ministry of Earth Sciences (MoES), Kochi, Government of India, for the support of crew ‘FORV Sagar Sampada’Funding was provided by the Centre for Marine Living Resources and Ecology (CMLRE), Ministry of Earth Sciences (MoES), Kochi, Government of India
文摘Two new free-living marine nematode species belonging to the genus Tricoma Cobb,1894(Desmoscolecidae)are identi-fied from the continental shelf region of the Bay of Bengal.Tricoma ajmalia sp.nov.is characterized by the number of main rings(84 male and 85 female),the arrangement of somatic setae,the head shape with broadly truncated end,the relatively long cephalic setae(69%-73%of corresponding head diameter),the amphids extending up to second main ring,slender spicules slightly curved and gu-berbaculum with dorsocaudally directed apophyses.The second new species,Tricoma sampadansis sp.nov.is characterized by the number of rings(64),the arrangement of somatic setae(14-13 subdorsal,16 subvenral),the head shape with broadly truncated end,the relatively long cephalic setae(75%corresponding head diameter),the amphidial fovea extending over first main ring,anterioirly bent spicules and gubernaculum with hooked proximal end.An updated valid species list of Tricoma is also presented.
文摘The interest in using the Datura stramonium plant is due to its natural products,which are used in many pharmaceutical industries.The objective of the current study was to assess the therapeutic and cytotoxic effects of the D.stramonium plant on two types of human cancer cell models(MCF7 and HT29)in vitro.A soxhlet apparatus was used to obtain methanolic extract from dried plant leaves.The recovered crude,after the solvent had evaporated,was then dispersed at varied concentrations of extract 100,50,20,and 0.0µg/mL and tested to see how the cells responded.Also,the cancer-testis antigen(CTA)gene transcription in the two cell types exposed to the plant extract was examined using a semi-quantitative real-time polymerase chain reaction.Gas chromatography–mass spectrometry(GC-MS)results produced the significant main metabolites Nonanoic acid,Tropine N-Oxide,3,6-Ditigloyloxy-7-hydroxytropane,Hexadecanoic acid,2-Pentadecanone,6,10,14-trimethyl-,Carvenone,methyl ester,Phytol,Aposcopolamine,Hyoscyamine,4,8,12,16-Tetramethylheptadecan-4-olide,Scopolamine,Alpha.-Tocospiro A,1,2-Cycloheptanedione,3,3,7,7-tetramethyl-,dihydrazone,Campesterol,Stigmasterol,Gamma-Sitosterol and dl-.alpha.-Tocopherol.The results showed that the two types of cell lines impacted by D.stramonium extract,through untreated type 1 cells(MCF7)gave a highly significant transcription according to all applicable genes.All implemented analyses cleared the strong genetic impacts of Datura extract on cancer cells’genomes.TGIF2LY and C2orf63 transcript accumulation were also significantly elevated when exposed to plant extract at a level of 50µg/mL in cell line type 2(HT29),but TGIF2LY and P53 had the lowest relative expression at a level of 100µg/mL when treated the same cell line type.
基金financed by the Hercules Foundation(project AKUL/13/47)funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 874837+2 种基金supported by the Flemish Government(department of Economy,Science and Innovation)through the Regenerative Medicine Crossing Borders(http://www.regmedxb.com)initiativeImages were recorded on a Zeiss LSM 780-SP Mai Tai HP DS(Cell and Tissue Imaging Cluster(CIC),Supported by Hercules AKUL/11/37 and FWO G.0929.15 to Pieter Vanden Berghe,University of Leuvensupported by Interne Fondsen KU Leuven/Internal Funds KU Leuven grant numbers C24M/22/058.
文摘Clinical translation of tissue-engineered advanced therapeutic medicinal products is hindered by a lack of patient-dependent and independent in-process biological quality controls that are reflective of in vivo outcomes.Recent insights into the mechanism of native bone repair highlight a robust path dependence.Organoid-based bottom-up developmental engineering mimics this pathdependence to design personalized living implants scaffold-free,with in-build outcome predictability.Yet,adequate(noninvasive)quality metrics of engineered tissues are lacking.Moreover,insufficient insight into the role of donor variability and biological sex as influencing factors for the mechanism toward bone repair hinders the implementation of such protocols for personalized bone implants.Here,male and female bone-forming organoids were compared to non-bone-forming organoids regarding their extracellular matrix composition,transcriptome,and secreted proteome signatures to directly link in vivo outcomes to quality metrics.As a result,donor variability in bone-forming callus organoids pointed towards two distinct pathways to bone,through either a hypertrophic cartilage or a fibrocartilaginous template.The followed pathway was determined early,as a biological sexdependent activation of distinct progenitor populations.Independent of donor or biological sex,a cartilage-to-bone transition was driven by a common panel of secreted factors that played a role in extracellular matrix remodeling,mineralization,and attraction of vasculature.Hence,the secreted proteome is a source of noninvasive biomarkers that report on biological potency and could be the missing link toward data-driven decision-making in organoid-based bone tissue engineering.
基金supported by the project from National Natural Science Foundation of China(31671962)Excellent Youth Foundation of Education Department of Hunan Province(23B0229)Fundamental Research Funds for the Central Universities(2662019PY034).
文摘Our previous study has demonstrated that procyanidin A_(1)(A_(1))and its simulated digestive product(D-A_(1))can prevent acrylamide(ACR)-induced cytotoxicity in small intestine cells.However,the potential mechanism remains poorly understood.In this study,ACR treatment was found to increase the levels of 8-hydroxy deoxyguanine(8-OHdG)and phosphorated histone H_(2)AX(γH_(2)AX),two DNA damage markers,thereby resulting in cell cycle arrest in the G2/M phase;whereas both A_(1) and D-A_(1) could prevent the phosphorylation of ataxia telangiectasia mutated(ATM)and checkpoint kinase 2(Chk2),and then regulate the expression of G2/M phase-related proteins,finally maintaining normal cell cycle progression.Moreover,A_(1) and D-A_(1) could increase the B cell lymphoma 2(Bcl-2)/Bcl2-associated X(Bax)ratio and decrease the expression of cleaved caspase-3 and cleaved caspase-9 proteins to alleviate ACR-induced cell apoptosis,which might be related to the inhibition of the mitogen-activated protein kinase(MAPK)pathway.More importantly,A_(1) showed no remarkable variation in inhibitory effect before and after digestion,indicating that it can endure gastrointestinal digestion and may be a promising phytochemical to alleviate ACR-induced intestinal cell damage.
