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2.
Med J Aust ; 221(1): 55-60, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38946642

RESUMO

OBJECTIVE: To assess the effectiveness of the Cultural, Social and Emotional Wellbeing Program for reducing psychological distress and enhancing the social and emotional wellbeing of Aboriginal women preparing for release from prison. STUDY DESIGN: Mixed methods; qualitative study (adapted reflexive thematic analysis of stories of most significant change) and assessment of psychological distress. SETTING, PARTICIPANTS: Aboriginal and Torres Strait Islander women at the Boronia Pre-release Centre for Women, Perth, Western Australia, May and July 2021. INTERVENTION: Cultural, Social and Emotional Wellbeing Program (two days per week for six weeks). The Program involves presentations, workshops, activities, group discussions, and self-reflections designed to enhance social and emotional wellbeing. MAIN OUTCOME MEASURES: Themes and subthemes identified from reflexive thematic analysis of participants' stories of most significant change; change in mean psychological distress, as assessed with the 5-item Kessler Scale (K-5) before and after the Program. RESULTS: Fourteen of 16 invited women completed the Program; ten participated in its evaluation. They reported improved social and emotional wellbeing, reflected as enhanced connections to culture, family, and community. Mean psychological distress was lower after the Program (mean K-5 score, 11.3; 95% confidence interval [CI], 9.0-13.6) than before the Program (9.0; 95% CI, 6.5-11.5; P = 0.047). CONCLUSION: The women who participated in the Program reported personal growth, including acceptance of self and acceptance and pride in culture, reflecting enhanced social and emotional wellbeing through connections to culture and kinship. Our preliminary findings suggest that the Program could improve the resilience of Aboriginal and Torres Strait Islander in contact with the justice system.


Assuntos
Saúde Mental , Havaiano Nativo ou Outro Ilhéu do Pacífico , Humanos , Feminino , Havaiano Nativo ou Outro Ilhéu do Pacífico/psicologia , Adulto , Saúde Mental/etnologia , Austrália Ocidental , Avaliação de Programas e Projetos de Saúde , Angústia Psicológica , Pesquisa Qualitativa , Pessoa de Meia-Idade , Emoções , Prisioneiros/psicologia , Estresse Psicológico/etnologia , Estresse Psicológico/psicologia , Adulto Jovem
3.
Soc Hist Med ; 37(1): 93-115, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38947278

RESUMO

This article explores the 'the moment of patient safety'-the period around 2000 when patient safety became a key policy concern of the British National Health Service (NHS), and other healthcare systems. While harm caused by medical care (iatrogenic injury) had long been acknowledged by clinicians and scientists, from 2000 a new systemic language of patient safety emerged in the NHS that promoted novel managerial and regulatory approaches to patient harm. This language reflected the state's increasing role in regulating healthcare, as well as the erosion of medical autonomy and the rise of new forms of bureaucratic management. Acknowledging a transnational, intellectual context behind the rise of policy interest in patient safety-for example, the application of insights from the industrial safety sciences-this article examines the role played by domestic cultural factors, such as medical negligence litigation and healthcare scandals, in helping to define the new language in Britain.

4.
Int J Eat Disord ; 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38949073

RESUMO

Using culture-based approaches, Monocello et al. revealed that young Korean men generally shared the same perceptions of fatness, including three categories ("too thin," "balanced," and "too fat"). The "balanced" category was most consistent with local South Korean culture, and the "too fat" category was associated with higher body dissatisfaction and disordered eating. Even though cultural differences in body ideals are an essential factor to consider in the development of body dissatisfaction and disordered eating, little research has applied culture-based approaches to explore body ideals in men, including how these ideals may be related to men's body image or eating behaviors. Thus, Monocello et al.'s work is a timely and vital contribution to the literature. In this commentary, we expand on Monocello et al.'s work by not only illustrating the roles of local cultures but also introducing the potential influences of external cultures via acculturation in shaping body ideals which, in turn, contribute to body dissatisfaction and disordered eating in men. We also provide future research directions to call for more culture-based research to understand body dissatisfaction and disordered eating among men in different cultural contexts.

5.
Methods Mol Biol ; 2833: 11-21, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38949696

RESUMO

In vitro biofilm models have allowed researchers to investigate the role biofilms play in the pathogenesis, virulence, and antimicrobial drug susceptibility of a wide range of bacterial pathogens. Rotary cell culture systems create three-dimensional cellular structures, primarily applied to eukaryotic organoids, that better capture characteristics of the cells in vivo. Here, we describe how to apply a low-shear, detergent-free rotary cell culture system to generate biofilms of Mycobacterium bovis BCG. The three-dimensional biofilm model forms mycobacterial cell aggregates in suspension as surface-detached biomass, without severe nutrient starvation or environmental stress, that can be harvested for downstream experiments. Mycobacterium bovis BCG derived from cell clusters display antimicrobial drug tolerance, presence of an extracellular matrix, and evidence of cell wall remodeling, all features of biofilm-associated bacteria that may be relevant to the treatment of tuberculosis.


Assuntos
Biofilmes , Mycobacterium bovis , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Mycobacterium bovis/crescimento & desenvolvimento , Mycobacterium bovis/efeitos dos fármacos , Mycobacterium bovis/fisiologia , Técnicas de Cultura de Células/métodos , Técnicas de Cultura de Células em Três Dimensões/métodos
6.
Front Bioeng Biotechnol ; 12: 1398052, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38952668

RESUMO

Electrical stimulation has emerged as a cornerstone technique in the rapidly evolving field of biomedical engineering, particularly within the realms of tissue engineering and regenerative medicine. It facilitates cell growth, proliferation, and differentiation, thereby advancing the development of accurate tissue models and enhancing drug-testing methodologies. Conductive hydrogels, which enable the conduction of microcurrents in 3D in vitro cultures, are central to this advancement. The integration of high-electroconductive nanomaterials, such as graphene oxide (GO), into hydrogels has revolutionized their mechanical and conductivity properties. Here, we introduce a novel electrostimulation assay utilizing a hybrid hydrogel composed of methacryloyl-modified small intestine submucosa (SIS) dECM (SISMA), chitosan methacrylate (ChiMA), and GO-polyethylene glycol (GO-PEG) in a 3D in vitro culture within a hypoxic environment of umbilical cord blood cells (UCBCs). Results not only demonstrate significant cell proliferation within 3D constructs exposed to microcurrents and early growth factors but also highlight the hybrid hydrogel's physiochemical prowess through comprehensive rheological, morphological, and conductivity analyses. Further experiments will focus on identifying the regulatory pathways of cells subjected to electrical stimulation.

7.
Biomater Adv ; 163: 213934, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38954877

RESUMO

Sample partitioning is a crucial step towards digitization of biological assays on polymer microfluidic platforms. However, effective liquid filling into microwells and long-term hydrophilicity remain a challenge in polymeric microfluidic devices, impeding the applicability in diagnostic and cell culture studies. To overcome this, a method to produce permanent superhydrophilic 3-dimensional microwells using cyclic olefin copolymer (COC) microfluidic chips is presented. The COC substrate is oxidized using UV treatment followed by ultrasonic spray coating of polyvinyl alcohol solution, offering uniform and long-term coating of high-aspect ratio microfeatures. The coated COC surfaces are UV-cured before bonding with a hydrophobic pressure-sensitive adhesive to drive selective filling into the wells. The surface hydrophilicity achieved using this method remains unchanged (water contact angle of 9°) for up to 6 months and the modified surface is characterized for physical (contact angle & surface energy, morphology, integrity of microfeatures and roughness), chemical composition (FTIR, Raman spectroscopy) and coating stability (pH, temperature, time). To establish the feasibility of the modified surface in biological applications, PVA-coated COC microfluidic chips are tested for DNA sensing (digital LAMP detection of CMV), and biocompatibility through protein adsorption and cell culture studies (cell adhesion, viability, and metabolic activity). Kidney and breast cells remained viable for the duration of testing (7 days) on this modified surface, and the coating did not affect the protein content, morphology or quality of the cultured cells. The ultrasonic spray coated system, coating with 0.25 % PVA for 15 cycles with 0.12 A current after UV oxidation, increased the surface energy of the COC (naturally hydrophobic) from 22.04 to 112.89 mJ/m2 and improved the filling efficiency from 40 % (native untreated COC) to 94 % in the microwells without interfering with the biocompatibility of the surface, proving to be an efficient, high-throughput and scalable method of microfluidic surface treatment for diagnostic and cell growth applications.

8.
Biofabrication ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38955197

RESUMO

Plasma cells (PCs) in bone marrow (BM) play an important role in both protective and pathogenic humoral immune responses, e.g., in various malignant and non-malignant diseases such as multiple myeloma (MM), primary and secondary immunodeficiencies and autoimmune diseases. Dedicated microenvironmental niches in the BM provide PCs with biomechanical and soluble factors that support their long-term survival. There is a high need for appropriate and robust model systems to better understand PCs biology, to develop new therapeutic strategies for PCs-related diseases and perform targeted preclinical studies with high predictive value. Most preclinical data have been derived from in vivo studies in mice, as in vitro studies of human PCs are limited due to restricted survival and functionality in conventional 2D cultures that do not reflect the unique niche architecture of the BM. We have developed a microphysiological, dynamic 3D BM culture system (BM-MPS) based on human primary tissue (femoral biopsies), mechanically supported by a hydrogel scaffold casing. While a bioinert agarose casing did not support PCs survival, a photo-crosslinked collagen-hyaluronic acid (Col-HA) hydrogel preserved the native BM niche architecture and allowed PCs survival in vitro for up to 2 weeks. Further, the Col-HA hydrogel was permissive to lymphocyte migration into the microphysiological system´s circulation. Long-term PCs survival was related to the stable presence in the culture of soluble factors, as APRIL, BAFF, and IL-6. Increasing immunoglobulins concentrations in the medium confirm their functionality over culture time. To the best of our knowledge, this study is the first report of successful long-term maintenance of primary-derived non-malignant PCs in vitro. Our innovative model system is suitable for in-depth in vitro studies of human PCs regulation and exploration of targeted therapeutic approaches such as CAR-T cell therapy or biologics.

9.
An Pediatr (Engl Ed) ; 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38955612

RESUMO

OBJECTIVE: To characterize safety incidents in paediatric emergency departments (PEDs): frequency, sources, root causes, and consequences. MATERIALS AND METHODS: We conducted a cross-sectional, observational and descriptive study in the PED of the Clinical University Hospital XX (blinded for review). Patients were recruited through opportunity sampling and the data were collected during care delivery and one week later through a telephone survey. The methodology was based on the ERIDA study on patient safety incidents related to emergency care, which in turn was based on the ENEAS and EVADUR studies. RESULTS: The study included a total of 204 cases. At least one incident was detected in 25 cases, with two incidents detected in 3 cases, for a total incidence of 12.3%. Twelve incidents were detected during care delivery and the rest during the telephone call. Ten percent did not reach the patient, 7.1% reached the patient but caused no harm, and 82.1% reached the patient and caused harm. Thirteen incidents (46.4%) did not have an impact on care delivery, 8 (28.6%) required a new visit or referral, 6 (21.4%) required additional observation and 1 (3.6%) medical or surgical treatment. The most frequent root causes were health care delivery and medication. Incidents related to procedures and medication were most frequent. Of all incidents, 78.6% were considered preventable, with 50% identified as clear failures in health care delivery. CONCLUSIONS: Safety incidents affected 12.3% of children managed in the PED of the HCUVA, of which 78.6% were preventable.

10.
BMC Prim Care ; 25(1): 234, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38951826

RESUMO

BACKGROUND: Urinary tract infections (UTI) affect almost two-thirds of all women during their lives and many experience recurrent infections. There are evidence-based guidelines from multiple international societies for evaluation and treatment; however, recent claims-based analyses have demonstrated that adherence to these guidelines is poor. This study seeks to understand the barriers experienced by U.S. primary care providers (PCPs) to providing guideline-based care for UTI and recurrent UTI (rUTI). METHODS: Semi-structured interviews of 18 PCPs, recruited from the greater Los Angeles area, examined real-world clinical management of UTI/rUTI episodes, decisions to refer to subspecialty care, and resources guiding counseling and management. Grounded theory methodology served to analyze interview transcripts and identify preliminary and major themes. RESULTS: Participants expressed the desire to obtain urine cultures for each cystitis episode, but felt pressured to make compromises by patient demands or barriers to care. PCPs had lower thresholds to empirical treatment if patients had a history of rUTIs, were elderly, or declined evaluation. Laboratory data was minimally utilized in clinical decision-making: urinalyses were infrequently considered when interpreting culture data. PCPs treated a broad set of urologic and non-urologic symptoms as UTI, even with negative cultures. PCPs did not feel comfortable initiating UTI prophylaxis, instead seeking specialist evaluation for anatomic causes. They were unaware of management guidelines, typically utilizing UpToDate® as their primary resource. Few evidence-based UTI prevention interventions were recommended by providers. CONCLUSIONS: Low availability of succinct and clear professional guidelines are substantial barriers to appropriate UTI/rUTI care. Poor useability of clinical guidance documents results in substantial confusion about the role of preventative measures and additional diagnostic testing. Difficulties in patient access to care providers lead to expectations for presumptive treatment. Future studies are needed to determine if improved educational materials for providers and/or management algorithms can improve guideline concordance of UTI management.


Assuntos
Atitude do Pessoal de Saúde , Fidelidade a Diretrizes , Médicos de Atenção Primária , Guias de Prática Clínica como Assunto , Pesquisa Qualitativa , Infecções Urinárias , Humanos , Infecções Urinárias/terapia , Médicos de Atenção Primária/psicologia , Feminino , Masculino , Recidiva , Pessoa de Meia-Idade , Adulto , Estados Unidos , Padrões de Prática Médica , Entrevistas como Assunto , Encaminhamento e Consulta
11.
Cureus ; 16(6): e61542, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38957255

RESUMO

Background The diagnosis of Mycobacterium avium-intracellulare complex lung disease (MAC-LD) requires two or more positive sputum cultures. Few reports have examined the usefulness of adding liquid culture to conventional solid culture for diagnosing MAC-LD. Methods A retrospective, cohort study of patients examined at Kurashiki Central Hospital in Japan with a confirmed diagnosis of MAC-LD between January 1, 2002, and June 20, 2021, was conducted. The primary endpoint was the culture positivity rate, which was compared between the liquid and Ogawa culture media in patients who underwent sputum culture using both methods. Secondary endpoints were the culture positivity rate in smear-positive specimens and the positivity rate by radiological type. Results The study, which involved 351 patients and 702 specimens, showed a higher positivity rate for liquid culture (n=690, 98.3%) than Ogawa culture (n=315, 44.9%). Overall, 265 patients (75.5%) would have had delayed MAC-LD diagnosis without liquid medium being used. Of the 95 smear-positive specimens, 71 (74.7%) were positive on both cultures, whereas 24 (25.3%) were positive only on liquid culture. The positivity rate of Ogawa culture varied by radiological type. Conclusions Liquid culture is more valuable for the early diagnosis of MAC-LD than Ogawa culture.

12.
Public Health Action ; 14(2): 51-55, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38957505

RESUMO

The occurrence of transient culture positivity for Mycobacterium tuberculosis (MTB), known as mirage de tuberculose, poses significant challenges in understanding its spectrum and implications. Here, we report a case of transient culture positivity, oscillating between detectable and non-detectable MTB cultures with minimal radiological features and review the literature on this phenomenon. The scarcity of scientific literature on this subject stems from the inherent impossibility of systematically studying mirage de tuberculose. Ethical and public health concerns prevent withholding treatment to monitor spontaneous reversion to negative cultures. Based on the literature, we estimate that mirage de tuberculose occurs in approximately one-third of individuals infected with MTB who exhibit no symptoms. Despite the inherently limited nature of these findings, they suggest that the significance of mirage de tuberculose may be greater than currently perceived. Managing cases of mirage de tuberculose presents formidable challenges from a public health perspective. Striking a balance between prompt treatment initiation to prevent transmission and the risk of unnecessary treatment requires careful consideration. In conclusion, mirage de tuberculose remains a poorly understood clinical entity with very limited literature available. Advancing research and interdisciplinary collaborations are essential to unravel the intricacies of this phenomenon and develop effective strategies to address its public health challenges.


L'apparition d'une culture transitoire positive pour Mycobacterium tuberculosis (MTB), connue sous le nom de mirage de tuberculose, pose des défis importants dans la compréhension de son spectre et de ses implications. Nous rapportons ici un cas de positivité transitoire des cultures, oscillant entre des cultures MTB détectables et non détectables avec des caractéristiques radiologiques minimales et passons en revue la littérature sur ce phénomène. La rareté de la littérature scientifique sur ce sujet provient de l'impossibilité inhérente d'étudier systématiquement le mirage de tuberculose. Des préoccupations éthiques et de santé publique empêchent l'interruption du traitement pour surveiller le retour spontané à des cultures négatives. Sur la base de la littérature, nous estimons que le mirage de tuberculose survient chez environ un tiers des personnes infectées par le MTB qui ne présentent aucun symptôme. Malgré la nature intrinsèquement limitée de ces résultats, ils suggèrent que l'importance du mirage de tuberculose pourrait être plus grande que ce que l'on perçoit actuellement. La prise en charge des mirages de tuberculose présente des défis considérables du point de vue de la santé publique. Il faut trouver un équilibre entre l'instauration rapide du traitement pour prévenir la transmission et le risque d'un traitement inutile. En conclusion, le mirage de tuberculose reste une entité clinique mal comprise et la littérature disponible est très limitée. L'avancement de la recherche et les collaborations interdisciplinaires sont essentiels pour démêler les subtilités de ce phénomène et élaborer des stratégies efficaces pour relever ses défis en matière de santé publique.

13.
Open Forum Infect Dis ; 11(7): ofae320, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38957687

RESUMO

Background: Direct whole genome sequencing (WGS) of Mycobacterium tuberculosis (Mtb) can be used as a tool to study drug resistance, mixed infections, and within-host diversity. However, WGS is challenging to obtain from clinical samples due to low number of bacilli against a high background. Methods: We prospectively collected 34 samples (sputum, n = 17; bronchoalveolar lavage, n = 13; and pus, n = 4) from patients with active tuberculosis (TB). Prior to DNA extraction, we used a ligand-mediated magnetic bead method to enrich Mtb from clinical samples and performed WGS on Illumina platform. Results: Mtb was definitively identified based on WGS from 88.2% (30/34) of the samples, of which 35.3% (12/34) were smear negative. The overall median genome coverage was 15.2% (interquartile range [IQR], 7.7%-28.2%). There was a positive correlation between load of bacilli on smears and genome coverage (P < .001). We detected 58 genes listed in the World Health Organization mutation catalogue in each positive sample (median coverage, 85% [IQR, 61%-94%]), enabling the identification of mutations missed by routine diagnostics. Mutations causing resistance to rifampicin, isoniazid, streptomycin, and ethambutol were detected in 5 of 34 (14.7%) samples, including the rpoB S441A mutation that confers resistance to rifampicin, which is not covered by Xpert MTB/RIF. Conclusions: We demonstrate the feasibility of magnetic bead-based enrichment for culture-free WGS of Mtb from clinical specimens, including smear-negative samples. This approach can also be integrated with low-cost sequencing workflows such as targeted sequencing for rapid detection of Mtb and drug resistance.

14.
Front Vet Sci ; 11: 1391872, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38957800

RESUMO

The effectiveness and safety of allogeneic mesenchymal stem/stromal cells (MSCs) can be affected by patient's immune recognition. Thus, MSC immunogenicity and their immunomodulatory properties are crucial aspects for therapy. Immune responses after allogeneic MSC administration have been reported in different species, including equine. Interactions of allogenic MSCs with the recipient's immune system can be influenced by factors like matching or mismatching for the major histocompatibility complex (MHC) between donor-recipient, and by the levels of MHC expression in MSCs. The latter can vary upon MSC inflammatory exposure or differentiation, such as chondrogenic induction, making both priming and differentiation interesting therapeutic strategies. This study investigated the systemic in vivo immune cellular response against allogeneic equine MSCs in these situations. Either MSCs in basal conditions (MSC-naïve), pro-inflammatory primed (MSC-primed) or chondrogenically differentiated (MSC-chondro) were repeatedly administered subcutaneously into autologous, MHC-matched or MHC-mismatched allogeneic equine recipients. At different time-points after each administration, lymphocytes were obtained from recipient horses and exposed in vitro to the same type of MSCs to assess the proliferative response of different T cell subsets (cytotoxic, helper, regulatory), B cells, and interferon gamma (IFNγ) secretion. Higher proliferative response of helper and cytotoxic T lymphocytes and IFNγ secretion was observed in response to all types of MHC-mismatched MSCs over MHC-matched ones. MSC-primed produced the highest immune response, followed by MSC-naïve, and MSC-chondro. However, MSC-primed activated Treg and had a mild effect on B cells, and the response after their second administration was similar to the first one. On the other hand, both MSC-chondro and MSC-naïve barely induced Treg response but promoted B lymphocyte activation, and proportionally induced a higher cell response after the second administration. In conclusion, both the type of MSC conditioning and the MHC compatibility influenced systemic immune recognition of equine MSCs after single and repeated administrations, but the response was different. Selecting MHC-matched donors would be particularly recommended for MSC-primed and repeated MSC-naïve administrations. While MHC-mismatching in MSC-chondro would be less critical, B cell response should not be ignored. Comprehensively investigating the in vivo immune response against equine allogeneic MSCs is crucial for advancing veterinary cell therapies.

15.
Front Psychol ; 15: 1392007, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38957879

RESUMO

Background: Psychological well-being (PWB) facilitates good health. Few studies have taken into consideration gender and how it can affect PWB within a sociocultural context. This study aims to determine if relationships between social, health, behavioral, and socioeconomic factors on PWB among older Taiwanese adults are affected by gender. Methods: Data were obtained from the 2016 Taiwan Mental Health Survey. A representative sample, of 2,286 individuals, was created using multistage proportional probability. Participants were interviewed at their homes using a structured questionnaire. Inclusion criteria were Taiwanese citizenship, age ≥ 55 years, and the ability to provide informed consent. Participants 65 years and above were selected for the study sample n = 1,533. An 18-item version of Ryff's PWB scale was used to determine PWB. The median value was used to categorize low and high PWB. Logistic regression analyses were used to examine predictors of PWB stratified by gender. Results: Chronic disease, unemployment, and financial dependence negatively impacted men's PWB. Satisfaction with living environment and family relationships positively impacted women's PWB. Unique characteristics of older men, women, and culture account for this. Conclusion: Gender-specific interventions aimed at promoting PWB in older adults are needed. Recommendations include educational programs, social support workshops, and community engagement initiatives.

16.
Biomater Adv ; 163: 213936, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38959652

RESUMO

Matrix stiffening is one of the major risk factors for hepatocellular carcinoma (HCC) and drives tumor progression. The extracellular matrix (ECM) stiffness of HCC displays mechanical heterogeneity, with stiffness increasing from the core to the invasive frontier. The distribution of liver cancer stem cells (CSCs) is related to this mechanical property. However, it is not sufficiently understood how heterogeneous matrix stiffness regulates the stemness of CSCs. In this study, we developed an adjustable gelatin/alginate hydrogel to investigate the effect of various matrix stiffnesses on CSC stemness under three-dimensional culture conditions. Gelatin/alginate hydrogel with the stiffness of soft (5 kPa), medium (16 kPa), and stiff (81 kPa) were prepared by altering the concentration of calcium ions. It was found that a stiffer matrix promoted stemness-associated gene expression, reduced drug sensitivity, enhanced sphere-forming and clonogenic ability, and tumorigenic potential. Mechanistically, matrix stiffening facilitates CSC stemness by increasing Yes-associated protein (YAP) activity and inhibiting Bcl-2 modifying factor (BMF) expression. Knockdown of YAP or overexpression of BMF significantly attenuated matrix stiffening-induced stemness, suggesting the involvement of YAP and BMF in this process. Together, our results unravel the regulatory mechanism of heterogeneous matrix stiffness on CSC stemness and also provide a novel therapeutic strategy for eradicating CSCs and improving the efficiency of HCC treatment.

17.
Sci Total Environ ; : 174345, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38960174

RESUMO

Seaweed cultivation can inhibit the occurrence of red tides. However, how seaweed aquaculture interactions with harmful algal blooms will be affected by the increasing occurrence and intensity of marine heatwaves (MHWs) is unknown. In this study, we run both monoculture and coculture systems to investigate the effects of a simulated heatwave on the competition of the economically important macroalga Gracilariopsis lemaneiformis against the harmful bloom diatom Skeletonema costatum. Coculture with G. lemaneiformis led to a growth decrease in S. costatum. Growth and photosynthetic activity (Fv/Fm) of G. lemaneiformis was greatly reduced by the heatwave treatment, and did not recover even after one week. Growth and photosynthetic activity of S. costatum was also reduced by the heatwave in coculture, but returned to normal during the recovery period. S. costatum also responded to the stressful environment by forming aggregates. Metabolomic analysis suggests that the negative effects on S. costatum were related to an allelochemical release from G. lemaneiformis. These findings show that MHWs may enhance the competitive advantages of S. costatum against G. lemaneiformis, leading to more severe harmful algal blooms in future extreme weather scenarios.

18.
Adv Protein Chem Struct Biol ; 141: 331-360, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38960479

RESUMO

We recently identified TMEM230 as a master regulator of the endomembrane system of cells. TMEM230 expression is necessary for promoting motor protein dependent intracellular trafficking of metalloproteins for cellular energy production in mitochondria. TMEM230 is also required for transport and secretion of metalloproteinases for autophagy and phagosome dependent clearance of misfolded proteins, defective RNAs and damaged cells, activities that decline with aging. This suggests that aberrant levels of TMEM230 may contribute to aging and regain of proper levels may have therapeutic applications. The components of the endomembrane system include the Golgi complex, other membrane bound organelles, and secreted vesicles and factors. Secreted cellular components modulate immune response and tissue regeneration in aging. Upregulation of intracellular packaging, trafficking and secretion of endosome components while necessary for tissue homeostasis and normal wound healing, also promote secretion of pro-inflammatory and pro-senescence factors. We recently determined that TMEM230 is co-regulated with trafficked cargo of the endomembrane system, including lysosome factors such as RNASET2. Normal tissue regeneration (in aging), repair (following injury) and aberrant destructive tissue remodeling (in cancer or autoimmunity) likely are regulated by TMEM230 activities of the endomembrane system, mitochondria and autophagosomes. The role of TMEM230 in aging is supported by its ability to regulate the pro-inflammatory secretome and senescence-associated secretory phenotype in tissue cells of patients with advanced age and chronic disease. Identifying secreted factors regulated by TMEM230 in young patients and patients of advanced age will facilitate identification of aging associated targets that aberrantly promote, inhibit or reverse aging. Ex situ culture of patient derived cells for identifying secreted factors in tissue regeneration and aging provides opportunities in developing therapeutic and personalized medicine strategies. Identification and validation of human secreted factors in tissue regeneration requires long-term stabile scaffold culture conditions that are different from those previously reported for cell lines used as cell models for aging. We describe a 3 dimensional (3D) platform utilizing non-biogenic and non-labile poly ε-caprolactone scaffolds that supports maintenance of long-term continuous cultures of human stem cells, in vitro generated 3D organoids and patient derived tissue. Combined with animal component free culture media, non-biogenic scaffolds are suitable for proteomic and glycobiological analyses to identify human factors in aging. Applications of electrospun nanofiber technologies in 3D cell culture allow for ex situ screening and the development of patient personalized therapeutic strategies and predicting their effectiveness in mitigating or promoting aging.


Assuntos
Envelhecimento , Organoides , Humanos , Organoides/metabolismo , Envelhecimento/metabolismo , Proteínas de Membrana/metabolismo , Senescência Celular , Feminino , Alicerces Teciduais/química , Glândulas Mamárias Humanas/metabolismo , Glândulas Mamárias Humanas/citologia
19.
Nature ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38961210
20.
J Sci Food Agric ; 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38963133

RESUMO

BACKGROUND: Yeast culture (YC) is a product fermented on a specific medium, which is a type of postbiotic of anaerobic solid-state fermentation. Although YC has positive effects on the animal growth and health, it contains a variety of beneficial metabolites as dark matter, which have not been quantified. In the present study, liquid chromatography-tandem mass spectrometry is employed to identify the unknown metabolites. Following their identification, the important chemicals are quantified using HPLC-diode array detection methods. RESULTS: Non-targeted metabolomics studies showed that 670 metabolites in total were identified in YC, of which 23 metabolites significantly increased, including organic acids, amino acids, nucleosides and purines, isoflavones, and other substances. The chemical quantitative analysis showed that the contents of succinic acid, aminobutyric acid, glutamine, purine and daidzein increased by 84.42%, 51.07%, 100%, 68.85% and 4.60%, respectively. CONCLUSION: Therefore, the use of non-targeted metabolomics combined with chemical quantitative analysis to reveal the nutritional and functional substances of YC could help to elucidate the postbiotic mechanism and provide theoretical support for the regulation of the directional accumulation of beneficial metabolites. © 2024 Society of Chemical Industry.

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