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1.
Sci Rep ; 14(1): 23147, 2024 10 04.
Artículo en Inglés | MEDLINE | ID: mdl-39366987

RESUMEN

Reprogrammed glucose metabolism is considered as the hallmark of cancer with therapeutic implications. Phytocompounds have potential to inhibit cancer metabolism. Here, we tested the ability of Withaferin A (WA), a withanolide derived from Withania somnifera, in modulating cancer metabolism. The assessed effect of WA on aerobic glycolysis in breast cancer cell lines showed that WA decreases the glucose uptake, lactate production and ATP generation by inhibiting the expression of key glycolytic enzymes i.e., GLUT1, HK2 and PKM2. We also identified that WA induced inhibition of cancer glycolysis by targeting c-myc as validated by silencing experiments followed by metabolic readouts. Decreased glycolysis resulted in reduced cell viability, biomass and colony forming ability of breast cancer cells. To further validate our in vitro findings in breast cancer patients, we analyzed 90 metabolic pathways in ~ 2000 breast tumors and observed that glycolysis is the most deregulated pathway in breast tumors. Deregulated glycolysis also predicted poor prognosis in breast cancer patients. In addition, patient data showed correlation between c-myc expression and glycolytic deregulation in breast cancer. Taken together, our results highlight the role of WA in inhibiting breast cancer metabolism via c-myc/glycolysis axis.


Asunto(s)
Neoplasias de la Mama , Glucólisis , Proteínas Proto-Oncogénicas c-myc , Witanólidos , Witanólidos/farmacología , Humanos , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Femenino , Glucólisis/efectos de los fármacos , Línea Celular Tumoral , Proteínas Proto-Oncogénicas c-myc/metabolismo , Glucosa/metabolismo , Supervivencia Celular/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos
2.
Endoscopy ; 2024 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-39401522

RESUMEN

The healthcare sector generates 8% of greenhouse emissions in the United States, of which GI endoscopy is the third largest contributor. Single-use tools are a major contributor to modifiable waste generation during GI (gastrointestinal) endoscopy. Through a quality improvement (QI) initiative, we aimed to reduce endoscopy waste by urging gastroenterologists to be mindful of the tools used during polypectomies and avoid using multiple tools. We discussed green endoscopy initiatives in monthly journal club and business meetings. Over 14 weeks, 210 patients were included in the pre-intervention and 112 in the post-intervention group. At baseline, 34% of colonoscopies required no intervention, 32% required one tool (either biopsy forceps or a snare) and 33% required multiple tools. After the intervention, the use of just one tool increased (17% increase, p<0.01) and the use of multiple tools decreased significantly (16% decrease p<0.01). The odds of using a single tool compared to multiple tools after the intervention was 2.98 (95% CI 1.6-5.53), p=0.005. This single-center QI study noted a significant change in practice patterns favoring using a single tool over multiple tools during colonoscopies after an environmentally conscious practice intervention was applied. This intervention can be readily applied to reduce endoscopy-related waste.

3.
MedEdPublish (2016) ; 14: 29, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39246526

RESUMEN

Introduction: Student centric learning approaches have been reported to be effective in introducing higher order cognitive skills required by the health professionals. However, learners' perceptions must be constructively aligned with new learning interventions to achieve a positive impact on their learning. The aim of this study was to explore the learning experiences of undergraduate dental students with case-based learning in orthodontics. Methods: A case-based learning model was introduced on orthodontic diagnosis and treatment planning for final year students on a Bachelor of Dentistry programme toward the end of their academic year. A survey was conducted to explore the perceptions and experiences of the participants. The research instrument was based on a previously validated questionnaire and included information on demographics and consisted of 12 items aimed at evaluating the benefits and challenges of cased based learning. Results: All 67 students in the final-year cohort participated in study, yielding a response rate of 100 percent. Participants across the board perceived CBL to be an effective strategy to learn the subject content and helpful in improving the students' skills in orthodontic diagnosis, treatment planning and team-working. CBL did not pose any significant challenges or barriers to student learning. Conclusion: Participants reported high acceptance of CBL in orthodontic teaching and learning and a positive impact on their educational experiences. CBL was perceived to be an appropriate strategy to enhance the diagnostic, treatment planning and team-working skills of dental students.

4.
BMC Plant Biol ; 24(1): 696, 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39044142

RESUMEN

BACKGROUND: Phosphorus (P) deficiency, a major nutrient stress, greatly hinders plant growth. Phosphate (Pi) uptake in plant roots relies on PHT1 family transporters. However, melon (Cucumis melo L.) lacks comprehensive identification and characterization of PHT1 genes, particularly their response patterns under diverse stresses. RESULTS: This study identified and analyzed seven putative CmPHT1 genes on chromosomes 3, 4, 5, 6, and 7 using the melon genome. Phylogenetic analysis revealed shared motifs, domain compositions, and evolutionary relationships among genes with close histories. Exon number varied from 1 to 3. Collinearity analysis suggested segmental and tandem duplications as the primary mechanisms for CmPHT1 gene family expansion. CmPHT1;4 and CmPHT1;5 emerged as a tandemly duplicated pair. Analysis of cis-elements in CmPHT1 promoters identified 14 functional categories, including putative PHR1-binding sites (P1BS) in CmPHT1;4, CmPHT1;6, and CmPHT1;7. We identified that three WRKY transcription factors regulated CmPHT1;5 expression by binding to its W-box element. Notably, CmPHT1 promoters harbored cis-elements responsive to hormones and abiotic factors. Different stresses regulated CmPHT1 expression differently, suggesting that the adjusted expression patterns might contribute to plant adaptation. CONCLUSIONS: This study unveils the characteristics, evolutionary diversity, and stress responsiveness of CmPHT1 genes in melon. These findings lay the foundation for in-depth investigations into their functional mechanisms in Cucurbitaceae crops.


Asunto(s)
Cucumis melo , Regulación de la Expresión Génica de las Plantas , Fosfatos , Filogenia , Proteínas de Plantas , Estrés Fisiológico , Cucumis melo/genética , Cucumis melo/metabolismo , Fosfatos/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estrés Fisiológico/genética , Genes de Plantas , Proteínas de Transporte de Fosfato/genética , Proteínas de Transporte de Fosfato/metabolismo , Transporte Biológico/genética
5.
J Clin Gastroenterol ; 2024 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-38546483

RESUMEN

BACKGROUND: Cystic fibrosis (CF) is a multisystem disorder that leads to abnormal transport of chloride and sodium across secretory epithelia resulting in thickened, viscous secretions in the bronchi, biliary tract, pancreas, intestine, and the reproductive system. Defects in the biliary tract can predispose to stone formation requiring endoscopic retrograde cholangiopancreatography (ERCP). However, there is a paucity of data assessing ERCP outcomes in patients with CF. METHODS: We identified patients from the Healthcare Cost and Utilization Project (HCUP)-National Inpatient Sample (NIS) between the years 2016 and 2020. Our study group included patients with CF of all ages who underwent an inpatient ERCP. We used ICD10 diagnostic and procedural codes to identify patients, procedures, and complications of the procedure. RESULTS: From 2016 to 2020, a total of 860,679 inpatient ERCPs were identified. Of these procedures, 535 (0.06%) were performed in patients with CF. The mean age of patients with CF undergoing ERCP was 60.62 years, of which 48% were males and 52% were females. Patients in the CF group had a higher incidence of post-ERCP pneumothorax (0.93%) than the patients in the non-CF group (0.15%). The occurrence of other ERCP-related adverse events was similar in both groups (P>0.05). On multivariate regression analysis, patients with CF were 1.75 times more likely to develop post-ERCP infections [odds ratio (OR): 1.75; 95% CI: 1.03-2.94; P=0.035) and 7.64 times more likely to develop post-ERCP pneumothorax (OR: 7.64; 95% CI: 1.03-56.5; P=0.046) compared to patients without CF after adjusting for confounders. The groups had no significant difference in mortality, post-ERCP pancreatitis, bleeding, perforation, pneumoperitoneum, and gas embolism. There was also no significant difference in the length of stay between the study and control groups. CONCLUSIONS: ERCP is a safe procedure in patients with CF with a comparable risk of postprocedural complications and mortality to those who do not have cystic fibrosis. However, patients with CF may experience a higher risk of post-ERCP infections and post-ERCP pneumothorax. Further studies are needed to prospectively evaluate outcomes of ERCP in patients with CF and to determine methods of mitigating adverse events.

6.
Cureus ; 16(2): e54942, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38544622

RESUMEN

Pulmonary alveolar microlithiasis (PAM) is an autosomal recessive disease of the lung, characterized by diffuse deposits of intra-alveolar calcium phosphate microliths. It usually affects both sexes, presenting mostly in the second and third decades. The clinical course is highly variable, ranging from being asymptomatic to respiratory failure. PAM is usually diagnosed after careful clinical, radiological, and pathological evaluation, usually when patients present for other medical purposes. Here, a case of PAM in a middle-aged man presenting with acute-on-chronic hypoxemic respiratory failure is reported, with a review of the literature.

7.
J Hazard Mater ; 470: 134130, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38555668

RESUMEN

Biogenic nanoparticle (NP), derived from plant sources, is gaining prominence as a viable, cost-effective, sustainable, and biocompatible alternative for mitigating the extensive environmental impact of arsenic on the interplay between plant-soil system. Herein, the impact of green synthesized zinc oxide nanoparticles (ZnONPs) was assessed on Catharanthus roseus root system-associated enzymes and their possible impact on microbiome niches (rhizocompartments) and overall plant performance under arsenic (As) gradients. The application of ZnONPs at different concentrations successfully modified the arsenic uptake in various plant parts, with the root arsenic levels increasing 1.5 and 1.4-fold after 25 and 50 days, respectively, at medium concentration compared to the control. Moreover, ZnONPs gradients regulated the various soil enzyme activities. Notably, urease and catalase activities showed an increase when exposed to low concentrations of ZnONPs, whereas saccharase and acid phosphatase displayed the opposite pattern, showing increased activities under medium concentration which possibly in turn influence the plant root system associated microflora. The use of nonmetric multidimensional scaling ordination revealed a significant differentiation (with a significance level of p < 0.05) in the structure of both bacterial and fungal communities under different treatment conditions across root associated niches. Bacterial and fungal phyla level analysis showed that Proteobacteria and Basidiomycota displayed a significant increase in relative abundance under medium ZnONPs concentration, as opposed to low and high concentrations, respectively. Similarly, in depth genera level analysis revealed that Burkholderia, Halomonas, Thelephora and Sebacina exhibited a notably high relative abundance in both the rhizosphere and rhizoplane (the former refers to the soil region influenced by root exudates, while the latter is the root surface itself) under medium concentrations of ZnONPs, respectively. These adjustments to the plant root-associated microcosm likely play a role in protecting the plant from oxidative stress by regulating the plant's antioxidant system and overall biomass.


Asunto(s)
Arsénico , Raíces de Plantas , Microbiología del Suelo , Contaminantes del Suelo , Contaminantes del Suelo/metabolismo , Arsénico/metabolismo , Arsénico/química , Raíces de Plantas/metabolismo , Raíces de Plantas/efectos de los fármacos , Catharanthus/metabolismo , Catharanthus/efectos de los fármacos , Tecnología Química Verde , Nanopartículas del Metal/química , Microbiota/efectos de los fármacos , Bacterias/metabolismo , Bacterias/efectos de los fármacos , Rizosfera
8.
ACS Appl Mater Interfaces ; 16(6): 7983-7995, 2024 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-38290481

RESUMEN

Developing a diffusion barrier layer on material interfaces has potential applications in various fields such as in packaging materials, pharmaceuticals, chemical filtration, microelectronics, and medical devices. Although numerous physical and chemical methods have been proposed to generate the diffusion barrier layer, the complexity of fabrication techniques and the high manufacturing costs limit their practical utility. Here, we propose an innovative approach to fabricate the diffusion barrier layer by irradiating poly(dimethylsiloxane) (PDMS) with a mid-infrared (λ = 10.6 µm) CO2 laser. This process directly creates a diffusion barrier layer on the PDMS surface by forming a heavily cross-linked network in the polymer matrix. The optimal irradiation conditions were investigated by modulating the defocusing distance, laser power, and number of scanning passes. The barrier thickness can reach up to 70 µm as observed by the scanning electron microscope (SEM). The attenuated total reflectance (ATR), electron dispersive X-ray (EDX), and X-ray photoelectron spectroscopy (XPS) analyses collectively confirmed the formation of the SiOx structure on the modified surface based on the decreased methyl group signal and the increased oxygen/silicon ratio. The diffusion test with the model drugs (rhodamine B and donepezil) demonstrated that the modified surface exhibits effective diffusion barrier properties and the rate of drug diffusion through the modified barrier layer can be controlled by the optimization of the irradiation parameters. This novel approach provides the possibility to develop a controllable diffusion barrier layer in a biocompatible polymer with prospective applications in the fields of pharmaceuticals, packing materials, and medical devices.

9.
Semin Cell Dev Biol ; 154(Pt C): 261-274, 2024 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-36379848

RESUMEN

Brain metastasis (BrM) is a major threat to the survival of melanoma, breast, and lung cancer patients. Circulating tumor cells (CTCs) cross the blood-brain barrier (BBB) and sustain in the brain microenvironment. Genetic mutations and epigenetic modifications have been found to be critical in controlling key aspects of cancer metastasis. Metastasizing cells confront inflammation and gradually adapt in the unique brain microenvironment. Currently, it is one of the major areas that has gained momentum. Researchers are interested in the factors that modulate neuroinflammation during BrM. We review here various epigenetic factors and mechanisms modulating neuroinflammation and how this helps CTCs to adapt and survive in the brain microenvironment. Since epigenetic changes could be modulated by targeting enzymes such as histone/DNA methyltransferase, deacetylases, acetyltransferases, and demethylases, we also summarize our current understanding of potential drugs targeting various aspects of epigenetic regulation in BrM.


Asunto(s)
Neoplasias Encefálicas , Neoplasias Pulmonares , Humanos , Epigénesis Genética , Enfermedades Neuroinflamatorias , Neoplasias Encefálicas/genética , Inflamación/genética , Microambiente Tumoral/genética
10.
Cureus ; 15(9): e46068, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37900471

RESUMEN

Disseminated histoplasmosis is a progressive granulomatous disease caused by Histoplasma capsulatum, which is an intracellular dimorphic fungus endemic to the Ohio and Mississippi River valleys in the United States. It is usually thought to be due to the failure of the activation of the T-cell-mediated immune response. Hemophagocytic lymphohistiocytosis (HLH) is a rare but potentially fatal condition, in which histiocytes and lymphocytes build up in and damage organs and other blood cells. We present a 37-year-old man with a past medical history of systemic lupus erythematosus (SLE) complicated by lupus nephritis on immunosuppressive therapy who presented to the emergency department with hypotension and was admitted for acute kidney injury. Prior to the presentation, he had persistent fever, myalgias, cough, mild shortness of breath, and back pain. Computed tomography (CT) chest shows "eggshell" calcification; microbiology evaluation of peripheral blood smear revealed intracellular organism, morphologically consistent with H. capsulatum; and urine histoplasmosis antigen test confirmed the diagnosis of histoplasmosis. HLH diagnosis was made clinically after "clinical and testing criteria" were evaluated. Despite further management, he developed coagulopathy and sepsis, which led to his death. At autopsy, we found organomegaly of the liver, spleen, and kidneys. Microscopically, these enlarged organs show old fibrotic granulomas and granulomatous inflammation with suspected fungal organisms. Gomori's methenamine silver special stain confirmed these fungal organisms to be consistent with Histoplasma species (3-5 micron budding yeasts). This case highlights that physicians should be aware of the diagnostic challenge that disseminated histoplasmosis with HLH could pose in a patient with SLE, especially in patients on immunosuppression. Failure to recognize the infection promptly could lead to grievous complications and possibly death.

11.
Sci Total Environ ; 904: 167226, 2023 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-37734611

RESUMEN

King grass has been recognized as a potential phytoremediation plant species due to its high biomass and resistance to heavy metals (HMs). However, the possible impacts of cadmium (Cd) contamination on rhizocompartments' microbial activities in association with king grass have not been extensively explored. The utilization of 16S rRNA gene and ITS sequencing was carried out to examine alterations in the bacterial and fungal communities in the rhizosphere and rhizoplane of king grass in response to low and high Cd stress. Results demonstrated that both bacterial and fungal communities' diversity and richness were negatively impacted by Cd stress, regardless of its concentration. However, evenness did not exhibit any significant response to either of the concentrations. Additionally, nonmetric multidimensional scaling (NMDS) ordination demonstrated a significant difference (p < 0.001) in microbial communities under different treatments. The abundance of bacterial taxa such as Steroibacter, Nitrospira, Pseudoxanthomonas, Cellvirio, Phenylobacterium, Mycobacterium, Pirellula and Aquicella was adversely affected under Cd stress while Flavobacterium, Gemmata, Thiobacillus and Gemmatimonas showed no prominent response, indicating their resistance to Cd stress. Like that, certain fungal taxa for instance, Cladosporium, Cercophora, Acremonium, Mortierella, Aspergillus, Penicillium, Glomus and Sebacina were also highly reduced by low and high Cd stress. In contrast, Fusarium, Thanatephorus, Botrytis and Curvularia did not show any response to Cd stress. The identified taxa may have a crucial role in the growth of king grass under heavy metal contamination, making them promising candidates for developing bioinoculants to encourage plant performance and phytoremediation capability in HM-contaminated soils.


Asunto(s)
Metales Pesados , Microbiota , Contaminantes del Suelo , Cadmio/toxicidad , Poaceae , Biodegradación Ambiental , ARN Ribosómico 16S , Suelo , Metales Pesados/toxicidad , Rizosfera , Bacterias , Microbiología del Suelo
12.
Heliyon ; 9(8): e18372, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37529340

RESUMEN

To address the gap of extant literature and to assess employees' in-role and innovative performance, a model was developed and tested through organizational justice facets- procedural, distributive, and interactional justice with knowledge hiding facets, well-being facets and professional commitment. The purpose of the present research is to inspect the role of justice facets in shaping knowledge hiding behavior through optimistic role of well-being toward employee performance with the remedial role of professional commitment under the shadow of Psychological Ownership Knowledge Theory (POKT) and Social Exchange Theory (SET). For that persistence, present research acknowledged the practices and connotations of knowledge hiding because limited research is prevailed on the contrasting influence of knowledge hiding practice. Data were collected through random sampling via dual-wave survey questionnaire from 613 employees working in Kuala Terengganu, Malaysia. Structural Equation Modeling was carried out through AMOS (24.0) and SPSS (25.0). Findings reveal that the association with in-role and innovative performance with justice is positively associated through well-being, and the relationship between knowledge hiding and job performance was also positively associated. This study argued that knowledge sharing reshapes knowledge hiding behavior that plays a negative role in organizational performance. This study suggested the notable contribution in the direction of organizational context of developing realm settings by revealing the predecessor character of knowledge hiding and endorses the organizational justice to persuade top management for in-role and innovative performance enhancement.

13.
Mol Cancer ; 22(1): 111, 2023 07 15.
Artículo en Inglés | MEDLINE | ID: mdl-37454123

RESUMEN

The diagnosis of brain metastasis (BrM) has historically been a dooming diagnosis that is nothing less than a death sentence, with few treatment options for palliation or prolonging life. Among the few treatment options available, brain radiotherapy (RT) and surgical resection have been the backbone of therapy. Within the past couple of years, immunotherapy (IT), alone and in combination with traditional treatments, has emerged as a reckoning force to combat the spread of BrM and shrink tumor burden. This review compiles recent reports describing the potential role of IT in the treatment of BrM in various cancers. It also examines the impact of the tumor microenvironment of BrM on regulating the spread of cancer and the role IT can play in mitigating that spread. Lastly, this review also focuses on the future of IT and new clinical trials pushing the boundaries of IT in BrM.


Asunto(s)
Neoplasias Encefálicas , Humanos , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/secundario , Inmunoterapia , Microambiente Tumoral
14.
Chemosphere ; 336: 139230, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37343643

RESUMEN

Chemical contamination or nutrient pollution is concerning for health, environmental, and economic reasons. Ecofriendly surface modification of nanoparticles is a consistent challenge for agricultural purposes. In response to this environmental concern, CuO-NPs synthesized through biological method using green source and characterized for morphological and structural features through SEM (scanning electron microscope) and TEM (transmission electron microscope) spectroscopy. Our research findings illustrate that the presence of salt stress induces a notable decline in both physiological and biochemical parameters within plants. Nevertheless, the utilization of T. harzianum and CuO-NPs exhibited a mitigating effect on the detrimental consequences induced by salt stress in plants. The application of T. harzianum and the simultaneous co-inoculation with CuO-NPs notably enhanced fresh biomass and facilitated vegetative growth in comparison to the control group. Furthermore, the exposure of both T. harzianum inoculum and Copper oxide nanoparticles resulted in a significant reduction of oxidative stresses, including reactive oxygen species (ROS) levels, H2O2, and lipid peroxidation (MDA) levels in the above-ground parts of the plant, while also minimizing electrolyte leakage (EL) by reducing root growth. Additionally, the co-inoculation of the endophyte and CuO-NPs led to a significant enhancement in antioxidant enzymatic activities, such as superoxide dismutase (SOD) and chitinase (CAT) activity in the above-ground parts, under salt stress conditions. The inoculum, along with its combination with CuO-NPs, decreased electrolyte conductivity and improved total chlorophyll contents as compared to the control. The combined application of T. harzianum and CuO-NPs improved salt tolerance in A. thaliana plants by triggering salt-associated gene expression. These findings suggest that the application of T. harzianum and CuO-NPs can considerably promote leaf anatomical changes in A. thaliana and have ability to enhance salt tolerance, particularly in saline areas.


Asunto(s)
Arabidopsis , Nanopartículas del Metal , Nanopartículas , Cobre/química , Peróxido de Hidrógeno/farmacología , Arabidopsis/metabolismo , Nanopartículas del Metal/toxicidad , Nanopartículas del Metal/química , Nanopartículas/toxicidad , Estrés Oxidativo , Estrés Salino
15.
J Hazard Mater ; 457: 131752, 2023 09 05.
Artículo en Inglés | MEDLINE | ID: mdl-37290353

RESUMEN

Microorganisms in the rhizosphere are crucial allies for plant stress tolerance. Recent research suggests that by interacting with the rhizosphere microbiome, microorganisms can aid in the revegetation of soils contaminated with heavy metal(loid)s (HMs). However, it is unknown that how Piriformospora indica influences the rhizosphere microbiome to mitigate arsenic-toxicity in arsenic-enriched environments. Artemisia annua plants were grown in the presence or absence of P. indica and spiked with low (50) and high (150 µmol/L) concentrations of arsenic (As). After inoculation with P. indica, fresh weight increased by 37.7% and 10% in control and high concentration treated plants, respectively. Transmission electron microscopy showed that cellular organelles were severely damaged by As and even disappeared under high concentration. Furthermore, As was mostly accumulated by 5.9 and 18.1 mg/kg dry weight in the roots of inoculated plants treated with low and high concentrations of As, respectively. Additionally, 16 S and ITS rRNA gene sequencing were applied to analyze the rhizosphere microbial community structure of A. annua under different treatments. A significant difference was observed in microbial community structure under different treatments as revealed by non-metric multidimensional scaling ordination. The bacterial and fungal richness and diversity in the rhizosphere of inoculated plants were actively balanced and regulated by P. indica co-cultivation. Lysobacter and Steroidobacter were found to be the As-resistant bacterial genera. We conclude that P. indica inoculation could alter rhizosphere microecology, thereby mitigating As-toxicity without harming the environment.


Asunto(s)
Arsénico , Artemisia annua , Microbiota , Arsénico/toxicidad , Artemisia annua/genética , Artemisia annua/microbiología , Raíces de Plantas/microbiología , Bacterias , Rizosfera , Microbiología del Suelo
16.
Mol Cancer ; 22(1): 1, 2023 01 04.
Artículo en Inglés | MEDLINE | ID: mdl-36597126

RESUMEN

BACKGROUND: Small cell lung cancer (SCLC) is an aggressive lung cancer subtype that is associated with high recurrence and poor prognosis. Due to lack of potential drug targets, SCLC patients have few therapeutic options. MicroRNAs (miRNAs) provide an interesting repertoire of therapeutic molecules; however, the identification of miRNAs regulating SCLC growth and metastasis and their precise regulatory mechanisms are not well understood. METHODS: To identify novel miRNAs regulating SCLC, we performed miRNA-sequencing from donor/patient serum samples and analyzed the bulk RNA-sequencing data from the tumors of SCLC patients. Further, we developed a nanotechnology-based, highly sensitive method to detect microRNA-1 (miR-1, identified miRNA) in patient serum samples and SCLC cell lines. To assess the therapeutic potential of miR-1, we developed various in vitro models, including miR-1 sponge (miR-1Zip) and DOX-On-miR-1 (Tet-ON) inducible stable overexpression systems. Mouse models derived from intracardiac injection of SCLC cells (miR-1Zip and DOX-On-miR-1) were established to delineate the role of miR-1 in SCLC metastasis. In situ hybridization and immunohistochemistry were used to analyze the expression of miR-1 and target proteins (mouse and human tumor specimens), respectively. Dual-luciferase assay was used to validate the target of miR-1, and chromatin immunoprecipitation assay was used to investigate the protein-gene interactions. RESULTS: A consistent downregulation of miR-1 was observed in tumor tissues and serum samples of SCLC patients compared to their matched normal controls, and these results were recapitulated in SCLC cell lines. Gain of function studies of miR-1 in SCLC cell lines showed decreased cell growth and oncogenic signaling, whereas loss of function studies of miR-1 rescued this effect. Intracardiac injection of gain of function of miR-1 SCLC cell lines in the mouse models showed a decrease in distant organ metastasis, whereas loss of function of miR-1 potentiated growth and metastasis. Mechanistic studies revealed that CXCR4 is a direct target of miR-1 in SCLC. Using unbiased transcriptomic analysis, we identified CXCR4/FOXM1/RRM2 as a unique axis that regulates SCLC growth and metastasis. Our results further showed that FOXM1 directly binds to the RRM2 promoter and regulates its activity in SCLC. CONCLUSIONS: Our findings revealed that miR-1 is a critical regulator for decreasing SCLC growth and metastasis. It targets the CXCR4/FOXM1/RRM2 axis and has a high potential for the development of novel SCLC therapies. MicroRNA-1 (miR-1) downregulation in the tumor tissues and serum samples of SCLC patients is an important hallmark of tumor growth and metastasis. The introduction of miR-1 in SCLC cell lines decreases cell growth and metastasis. Mechanistically, miR-1 directly targets CXCR4, which further prevents FOXM1 binding to the RRM2 promoter and decreases SCLC growth and metastasis.


Asunto(s)
Neoplasias Pulmonares , MicroARNs , Carcinoma Pulmonar de Células Pequeñas , Humanos , Animales , Ratones , Carcinoma Pulmonar de Células Pequeñas/genética , Carcinoma Pulmonar de Células Pequeñas/patología , MicroARNs/genética , MicroARNs/metabolismo , Línea Celular Tumoral , Neoplasias Pulmonares/patología , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Proteína Forkhead Box M1/genética , Receptores CXCR4/genética , Receptores CXCR4/metabolismo
17.
Int J Mol Sci ; 23(20)2022 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-36292929

RESUMEN

Phosphate (Pi) deficiency is a common phenomenon in agricultural production and limits plant growth. Recent work showed that long-term Pi deficiency caused the inhibition of photosynthesis and inefficient electron transport. However, the underlying mechanisms are still unknown. In this study, we used the physiological, histochemical, and transcriptomic methods to investigate the effect of low-Pi stress on photosynthetic gas exchange parameters, cell membrane lipid, chloroplast ultrastructure, and transcriptional regulation of key genes in melon seedlings. The results showed that Pi deficiency significantly downregulated the expression of aquaporin genes, induced an increase in ABA levels, and reduced the water content and free water content of melon leaves, which caused physiological drought in melon leaves. Therefore, gas exchange was disturbed. Pi deficiency also reduced the phospholipid contents in leaf cell membranes, caused the peroxidation of membrane lipids, and destroyed the ultrastructure of chloroplasts. The transcriptomic analysis showed that 822 differentially expressed genes (DEGs) were upregulated and 1254 downregulated by Pi deficiency in leaves. GO and KEGG enrichment analysis showed that DEGs significantly enriched in chloroplast thylakoid membrane composition (GO:0009535), photosynthesis-antenna proteins (map00196), and photosynthesis pathways (map00195) were downregulated by Pi deficiency. It indicated that Pi deficiency regulated photosynthesis-related genes at the transcriptional level, thereby affecting the histochemical properties and physiological functions, and consequently causing the reduced light assimilation ability and photosynthesis efficiency. It enriches the mechanism of photosynthesis inhibition by Pi deficiency.


Asunto(s)
Cucumis melo , Cucumis melo/genética , Transcriptoma , Fotosíntesis/genética , Hojas de la Planta/metabolismo , Fosfatos/metabolismo , Agua/metabolismo , Lípidos de la Membrana/metabolismo , Fosfolípidos/metabolismo
18.
Cureus ; 14(8): e28600, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36185892

RESUMEN

Dengue virus can co-infect with a number of viruses, bacteria, and parasites of which dengue malaria co-infection is most well-known. We report a rare case of dengue virus co-infection with typhoid fever and the development of dengue hemorrhagic fever (DHF) during a dengue outbreak. The second spike of high-grade fever following initial defervescence with antibiotic therapy, hemorrhagic manifestations, new onset leucopenia and thrombocytopenia, and evidence of plasma leakage raised suspicion of DHF. Diagnosis of dengue co-infection was made by seroconversion for anti-dengue immunoglobulin M (IgM) antibodies by enzyme-linked immunosorbent assay (ELISA) on the seventh day of new-onset fever. Early recognition and judicious use of fluid therapy prevented the patient from developing shock and its complications. Prompt diagnosis, early recognition of plasma leakage, and appropriate management of DHF can reduce morbidity and mortality.

19.
Eval Health Prof ; 45(3): 313-324, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35794858

RESUMEN

COVID-19 rapidly spread across the world, constituting a public health disaster unlike any other experienced in decades. The impact exerted on workplaces and their employees was dramatic, and an immense burden fell on healthcare provision globally. Along with "front-line" healthcare staff, sanitation workers at hospitals also had to cope with additional workloads, making them vulnerable to psychological trauma and affecting their quality of life at establishments. This study investigated how the factors of occupational stress, self-efficacy (belief in the capacity to carry out a task well) and mental health altered the WRQoL (Work-Related Quality of Life) of employees carrying out sanitation duties at hospitals in Malaysia. To this end, a survey translated into the Malay language was conducted among 449 such workers during a so-called "recovery movement control order", i.e. quarantine and control measures pertaining to an outbreak of Coronavirus disease. Research involved co-variance-based structural equation modeling, performed in IBM-AMOS-26 software, in order to discern the causal relationship of the aforementioned factors on WRQoL. Results revealed a high level of occupational stress, diminished self-efficacy and poor mental health among the employees surveyed. Such stress directly impacted the WRQoL of the second factor alongside an indirect effect on that of the third, i.e. anxiety stemming from potentially catching the virus and the experience of having to disinfect facilities for treating patients, undertake cleaning duties, and move corpses.


Asunto(s)
COVID-19 , Estrés Laboral , COVID-19/epidemiología , Hospitales , Humanos , Malasia/epidemiología , Salud Mental , Estrés Laboral/epidemiología , Pandemias , Calidad de Vida , Saneamiento , Autoeficacia
20.
Front Psychol ; 13: 833627, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35693527

RESUMEN

The unsettling fear of COVID-19 infections has caused a new trend in consumer behavior in the food and beverage industry. The unprecedented COVID-19 pandemic has shifted consumers' preferences from eat-in to online delivery. This research aims to measure the impact of consumers' motivation to protect themselves from contracting COVID-19, which explains why people switch from eat-in to online food delivery. We adopted the theory of protection motivation (PMT) to explain consumer switching behavior during the COVID-19 pandemic. The present study investigated the mediating effect of switching intention on the relationship between vulnerability, altruistic fear, anticipated regret, and switching behavior. Simultaneously, we examined the role of brand awareness as a moderator of behavioral choices of consumers switching from eat-in to online delivery. We collected data from 681 eatery consumers in Kuala Terengganu, Malaysia, using scenario-based survey questionnaires (327 eat-in respondents and 354 online delivery respondents). Then, the data were analyzed using structural equation modeling (SEM). This new generation analysis was conducted using the analysis of moment structure (AMOS) (v.24.0) and the statistical package for social science (SPSS-version 25.0). The results indicated that consumer vulnerability, altruistic fear, and anticipated regret of COVID-19 increased consumers' propensity to shift from eat-in to online food delivery. Allegedly, consumer behavioral control and intention of switching toward online delivery were pointedly affected by switching behavior. The results indicated that consumer vulnerability, altruistic fear, and anticipated regret of COVID-19 increased the shifting of restaurant dine-in patterns and made the intention to switch to online delivery. Consumers' alleged behavioral control and their intention of switching toward online delivery were pointedly affected by switching behavior. We also found that brand awareness moderately affects switching behavior toward restaurant settings. The present research contributes to developing the consumer behavior model of switching from eat-in to online delivery. This study also provides eatery customers and the business community with a safer and healthier proposition of shifting to online food delivery during the pandemic.

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