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1.
Int J Pharm ; : 124450, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38986968

RESUMO

Wounds pose a formidable challenge in healthcare, necessitating the exploration of innovative tissue-healing solutions. Traditional wound dressings exhibit drawbacks, causing tissue damage and impeding natural healing. Using a Microwave (MW)-)-assisted technique, we envisaged a novel hydrogel (Hg) scaffold to address these challenges. This hydrogel scaffold was created by synthesizing a pH-responsive crosslinked material, specifically locust bean gum-grafted-poly(acrylamide-co-acrylic acid) [LBG-g-poly(AAm-co-AAc)], to enable sustained release of c-phycocyanin (C-Pc). Synthesized LBG-g-poly(AAm-co-AAc) was fine-tuned by adjusting various synthetic parameters, including the concentration of monomers, duration of reaction, and MW irradiation intensity, to maximize the yield of crosslinked LBG grafted product and enhance encapsulation efficiency of C-Pc. Following its synthesis, LBG-g-poly(AAm-co-AAc) was thoroughly characterized using advanced techniques, like XRD, TGA, FTIR, NMR, and SEM, to analyze its structural and chemical properties. Moreover, the study examined the in-vitro C-Pc release profile from LBG-g-poly(AAm-co-AAc) based hydrogel (HgCPcLBG). Findings revealed that the maximum release of C-Pc (64.12 ±â€¯2.69 %) was achieved at pH 7.4 over 48 h. Additionally, HgCPcLBG exhibited enhanced antioxidant performance and compatibility with blood. In vivo studies confirmed accelerated wound closure, and ELISA findings revealed reduced inflammatory markers (IL-6, IL-1ß, TNF-α) within treated skin tissue, suggesting a positive impact on injury repair. A low-cost and eco-friendly approach for creating LBG-g-poly(AAm-co-AAc) and HgCPcLBG has been developed. This method achieved sustained release of C-Pc, which could be a significant step forward in wound care technology.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38833068

RESUMO

A prolonged and compromised wound healing process poses a significant clinical challenge, necessitating innovative solutions. This research investigates the potential application of nanotechnology-based formulations, specifically nanofiber (NF) scaffolds, in addressing this issue. The study focuses on the development and characterization of multifunctional nanofibrous scaffolds (AZL-CS/PVA-NF) composed of azilsartan medoxomil (AZL) enriched chitosan/polyvinyl alcohol (CS/PVA) through electrospinning. The scaffolds underwent comprehensive characterization both in vitro and in vivo. The mean diameter and tensile strength of AZL-CS/PVA-NF were determined to be 240.42 ± 3.55 nm and 18.05 ± 1.18 MPa, respectively. A notable drug release rate of 93.86 ± 2.04%, was observed from AZL-CS/PVA-NF over 48 h at pH 7.4. Moreover, AZL-CS/PVA-NF exhibited potent antimicrobial efficacy for Staphylococcus aureus and Pseudomonas aeruginosa. The expression levels of Akt and CD31 were significantly elevated, while Stat3 showed a decrease, indicating a heightened tissue regeneration rate with AZL-CS/PVA-NF compared to other treatment groups. In vivo ELISA findings revealed reduced inflammatory markers (IL-6, IL-1ß, TNF-α) within treated skin tissue, implying a beneficial effect on injury repair. The comprehensive findings of the present endeavour underscore the superior wound healing activity of the developed AZL-CS/PVA-NF scaffolds in a Wistar rat full-thickness excision wound model. This indicates their potential as novel carriers for drugs and dressings in the field of wound care.

3.
Am J Ther ; 31(3): e258-e267, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38691665

RESUMO

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is characterized by loss of motor neurons due to degeneration of nerve cells within the brain and spinal cord. Early symptoms include limb weakness, twitching or muscle cramping, and slurred speech. As the disease progresses, difficulty breathing, swallowing, and paralysis can lead to death. Currently, there are no medications that cure ALS, and guidelines recommend treatments focused on symptom management. Intravenous (IV) edaravone was approved by the US Food and Drug Administration (FDA) in 2017 as a treatment to slow the progression of ALS. In May 2022, the FDA approved an oral suspension (ORS) formulation of edaravone. MECHANISM OF ACTION: The mechanism of action of edaravone is not well defined. However, its neuroprotective effects are thought to result from antioxidant properties occurring through elimination of free radicals. PHARMACOKINETICS: Edaravone ORS (105 mg) has a bioavailability of 57% when compared with edaravone IV (60 mg). The ORS should be taken on an empty stomach in the morning, with water and no food or beverages, for 1 hour. Edaravone is bound to albumin (92%), has a mean volume of distribution of 63.1 L, a half-life of 4.5-9 hours, and a total clearance of 35.9 L/h after intravenous administration. Edaravone is metabolized into nonactive sulfate and glucuronide conjugates. CLINICAL TRIALS: The FDA approval was based on studies of the pharmacokinetics, safety, tolerability, and bioavailability of edaravone ORS. A phase III, global, multicenter, open-label safety study was conducted on edaravone ORS in 185 patients with ALS over 48 weeks. The most reported treatment-emergent adverse events were falls, muscular weakness, and constipation. Serious treatment-emergent adverse events included disease worsening, dysphagia, dyspnea, and respiratory failure. THERAPEUTIC ADVANCE: Oral edaravone is an ALS treatment that can be self-administered or administered by a caregiver, precluding the need for administration by a health care professional in an institutional setting.


Assuntos
Esclerose Lateral Amiotrófica , Edaravone , Fármacos Neuroprotetores , Edaravone/administração & dosagem , Edaravone/farmacologia , Edaravone/uso terapêutico , Humanos , Esclerose Lateral Amiotrófica/tratamento farmacológico , Fármacos Neuroprotetores/administração & dosagem , Fármacos Neuroprotetores/uso terapêutico , Fármacos Neuroprotetores/efeitos adversos , Administração Oral , Suspensões , Disponibilidade Biológica
4.
Inorg Chem ; 63(17): 7754-7769, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38625043

RESUMO

The reactivity of six MnIV-oxo complexes in C-H bond oxidation has been examined using a combination of kinetic experiments and computational methods. Variable-temperature studies of the oxidation of 9,10-dihydroanthracene (DHA) and ethylbenzene by these MnIV-oxo complexes yielded activation parameters suitable for evaluating electronic structure computations. Complementary kinetic experiments of the oxidation of deuterated DHA provided evidence for hydrogen-atom tunneling in C-H bond oxidation for all MnIV-oxo complexes. These results are in accordance with the Bell model, where tunneling occurs near the top of the transition-state barrier. Density functional theory (DFT) and DLPNO-CCSD(T1) computations were performed for three of the six MnIV-oxo complexes to probe a previously predicted multistate reactivity model. The DFT computations predicted a thermal crossing from the 4B1 ground state to a 4E state along the C-H bond oxidation reaction coordinate. DLPNO-CCSD(T1) calculations further confirm that the 4E transition state offers a lower energy barrier, reinforcing the multistate reactivity model for these complexes. We discuss how this multistate model can be reconciled with recent computations that revealed that the kinetics of C-H bond oxidation by this set of MnIV-oxo complexes can be well-predicted on the basis of the thermodynamic driving force for these reactions.

5.
Sci Rep ; 14(1): 9865, 2024 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-38684815

RESUMO

Weight change trajectory from diet and lifestyle interventions typically involves rapid weight loss followed by a weight plateau after approximately 6 months. Changing from one weight-loss diet to another at the time of the plateau could instigate renewed weight loss. Therefore, our secondary analysis aimed to assess trajectory of weight loss in a 12-month, randomized, cross-over study. Forty-two adults were randomized to eat a healthy low-fat or healthy low-carbohydrate diet for 6 months then switched to the opposite diet for an additional 6 months. Regardless of diet assignment, participants experienced rapid initial weight loss, which slowed between 3 to 6 months. After switching diets at 6 months, weight modestly decreased until 9 months, but at a rate slower than the initial 3 months and slower than the rate from 3 to 6 months. This suggests that the weight loss plateau typically seen at 6 months is physiological and cannot be overcome by simply switching to a different weight-loss diet.


Assuntos
Estudos Cross-Over , Redução de Peso , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Dieta com Restrição de Carboidratos/métodos , Dieta Redutora/métodos , Obesidade/dietoterapia , Dieta com Restrição de Gorduras
6.
J Arthroplasty ; 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38657914

RESUMO

BACKGROUND: Despite an increase in outpatient total hip arthroplasty (THA) and total knee arthroplasty (TKA), large-scale data are lacking on current practice for antibiotic prophylaxis prescribing. We aimed to describe current oral antibiotic prophylaxis practices nationally for outpatient THA and TKA. METHODS: This nationwide retrospective cohort study included primary outpatient THA or TKA procedures in patients aged 18 to 64 years from 2018 to 2021 using a national claims database. Oral antibiotic prescriptions filled perioperatively (defined as 5 days before to 3 days after surgery) were extracted; these were categorized and assumed to represent postoperative prophylaxis. Multivariable logistic regression measured associations between patient and surgery characteristics and perioperative oral antibiotic prophylaxis. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) are reported. RESULTS: Oral antibiotic prescriptions were filled in 16.5% of 73,015 outpatient THA and TKA (18.4% of 24,857 THAs, 15.5% of 48,158 TKAs) procedures. Prescriptions were most often for cephalosporins (74.3%), with cephalexin (52.8%), and cefadroxil (19.1%) being the most common. Non-cephalosporin antibiotics prescribed were mainly clindamycin (6.8%), sulfamethoxazole-trimethoprim (6.7%), and doxycycline (6.2%). The odds of receiving oral antibiotic prophylaxis were higher for THA compared to TKA (OR 1.13, 95% CI 1.09 to 1.18, P < .001) and in the presence of obesity, diabetes, and autoimmune conditions (OR 1.08 to 1.13, P < .001 to .01). Ambulatory surgery center procedures also had significantly increased odds of prophylaxis compared to hospital-based outpatient surgeries (OR 2.62, 95% CI 2.51 to 2.73, P < .001). Additionally, regional and time-based variations were noted. CONCLUSIONS: Perioperative oral antibiotic prophylaxis prescriptions were filled in only 16.5% of outpatient THA and TKA cases, with variation in the type of antibiotic prescribed. The receipt of any prophylaxis and specific medications was associated with demographic, clinical, and procedure-related characteristics. Follow-up research will evaluate associations with infection risk reduction.

7.
Transl Res ; 268: 63-78, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38499286

RESUMO

Cisplatin alone or in combination with 5FU and docetaxel is the preferred chemotherapy regimen for advanced-stage OSCC patients. However, its use has been linked to recurrence and metastasis due to the development of drug resistance. Therefore, sensitization of cancer cells to conventional chemotherapeutics can be an effective strategy to overcome drug resistance. Piperlongumine (PL), an alkaloid, have shown anticancer properties and sensitizes numerous neoplasms, but its effect on OSCC has not been explored. However, low aqueous solubility and poor pharmacokinetics limit its clinical application. Therefore, to improve its therapeutic efficacy, we developed piperlongumine-loaded PLGA-based smart nanoparticles (smart PL-NPs) that can rapidly release PL in an acidic environment of cancer cells and provide optimum drug concentrations to overcome chemoresistance. Our results revealed that smart PL-NPs has high cellular uptake in acidic environment, facilitating the intracellular delivery of PL and sensitizing cancer cells to cisplatin, resulting in synergistic anticancer activity in vitro by increasing DNA damage, apoptosis, and inhibiting drug efflux. Further, we have mechanistically explored the Hippo-YAP signaling pathway, which is the critical mediator of chemoresistance, and investigated the chemosensitizing effect of PL in OSCC. We observed that PL alone and in combination with cisplatin significantly inhibits the activation of YAP and its downstream target genes and proteins. In addition, the combination of cisplatin with smart PL-NPs significantly inhibited tumor growth in two preclinical models (patient-derived cell based nude mice and zebrafish xenograft). Taken together, our findings suggest that smart PL-NPs with cisplatin will be a novel formulation to reverse cisplatin resistance in patients with advanced OSCC.


Assuntos
Cisplatino , Dioxolanos , Resistencia a Medicamentos Antineoplásicos , Via de Sinalização Hippo , Neoplasias Bucais , Nanopartículas , Proteínas Serina-Treonina Quinases , Transdução de Sinais , Humanos , Cisplatino/farmacologia , Nanopartículas/química , Dioxolanos/farmacologia , Dioxolanos/administração & dosagem , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Animais , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/patologia , Neoplasias Bucais/metabolismo , Linhagem Celular Tumoral , Transdução de Sinais/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/metabolismo , Peixe-Zebra , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/metabolismo , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Fatores de Transcrição/metabolismo , Camundongos Nus , Camundongos , Proteínas de Sinalização YAP , Ensaios Antitumorais Modelo de Xenoenxerto , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Piperidonas
8.
J Acad Nutr Diet ; 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38423509

RESUMO

BACKGROUND: The Healthy Eating Index 2010 (HEI-2010) and Alternative Healthy Eating Index 2010 (AHEI-2010) are commonly used to measure dietary quality in research settings. Neither index is designed specifically to compare diet quality between low-carbohydrate (LC) and low-fat (LF) diets. It is unknown whether biases exist in making these comparisons. OBJECTIVE: The aim was to determine whether HEI-2010 and AHEI-2010 contain biases when scoring LC and LF diets. DESIGN: Secondary analyses of the Diet Intervention Examining the Factors Interacting With Treatment Success (DIETFITS) weight loss trial were conducted. The trial was conducted in the San Francisco Bay Area of California between January 2013 and May 2016. Three approaches were used to investigate whether biases existed for HEI-2010 and AHEI-2010 when scoring LC and LF diets. PARTICIPANTS/SETTING: DIETFITS participants were assigned to follow healthy LC or healthy LF diets for 12 months (n = 609). MAIN OUTCOMES MEASURES: Mean diet quality index scores for each diet were measured. STATISTICAL ANALYSIS: Approach 1 examined both diet quality indices' scoring criteria. Approach 2 compared scores garnered by exemplary quality LC and LF menus created by registered dietitian nutritionists. Approach 3 used 2-sided t tests to compare the HEI-2010 and AHEI-2010 scores calculated from 24-hour dietary recalls of DIETFITS trial participants (n = 608). RESULTS: Scoring criteria for both HEI-2010 (100 possible points) and AHEI-2010 (110 possible points) were estimated to favor an LF diet by 10 points. Mean scores for exemplary quality LF menus were higher than for LC menus using both HEI-2010 (91.8 vs 76.8) and AHEI-2010 (71.7 vs 64.4, adjusted to 100 possible points). DIETFITS participants assigned to a healthy LF diet scored significantly higher on HEI and AHEI than those assigned to a healthy LC diet at 3, 6, and 12 months (all, P < .001). Mean baseline scores were lower than mean scores at all follow-up time points regardless of diet assignment or diet quality index used. CONCLUSIONS: Commonly used diet quality indices, HEI-2010 and AHEI-2010, showed biases toward LF vs LC diets. However, both indices detected expected changes in diet quality within each diet, with HEI-2010 yielding greater variation in scores. Findings support the use of these indices in measuring diet quality differences within, but not between, LC and LF diets.

9.
J Adolesc Health ; 74(5): 1026-1032, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38323963

RESUMO

PURPOSE: Gaps still exist in medical education about the sexual health needs of sexual diverse populations, and little is known about how translatable current learning modules are to patient encounters. Efforts at an academic medical institution have been made to address this need, including a two-hour adolescent sexuality workshop during the Core Clerkship in Pediatrics. This workshop's efficacy was evaluated in an objective structured clinical examination (OSCE) given to rising fourth-year medical students, where the standardized patient case focused on an adolescent cisgender male with dysuria and in a new, same-sex relationship. METHODS: Performance of students who completed the workshop prior to the OSCE (n = 48) were compared to those of students who did not participate in the workshop prior to the OSCE (n = 17). The encounters were recorded and transcribed, and the deidentified transcripts were scored on a rubric focusing on five domains: sexual identity disclosure, behavioral assessment, psychosocial history, counseling and anticipatory guidance, and relationship building. RESULTS: Student's t-test comparison of the scores found significantly higher scores for the psychosocial history domain (p = .04), particularly concerning disclosure of a new boyfriend and recent sexual activity (p = .008), for students who had the workshop before the OSCE. DISCUSSION: Students who took the adolescent sexuality workshop performed better in gathering psychosocial information in an OSCE encounter a sexual minority adolescent. These results affirm prior work that active learning on sexual diverse health in medical school curricula may prepare students for effective engagement with adolescents exploring their sexuality.


Assuntos
Educação de Graduação em Medicina , Educação Médica , Estudantes de Medicina , Humanos , Masculino , Adolescente , Criança , Educação Sexual , Estudantes de Medicina/psicologia , Educação de Graduação em Medicina/métodos , Comunicação , Competência Clínica , Avaliação Educacional
10.
Int J Biol Macromol ; 263(Pt 2): 130517, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38423444

RESUMO

Orally targeted delivery systems have attracted ample interest in colorectal cancer management. In this investigation, we developed Inositol hexaphosphate (IHP) loaded Tripolyphosphate (Tr) crosslinked Pectin (Pe) Chitosan (Ch) nanoparticles (IHP@Tr*Pe-Ch-NPs) and modified them with l-Carnitine (CE) (CE-IHP@Tr*Pe-Ch-NPs) to improve uptake in colon cells. The formulated CE-IHP@Tr*Pe-Ch-NPs displayed a monodisperse distribution with 219.3 ± 5.5 nm diameter and 30.17 mV surface charge. Cell-line studies revealed that CE-IHP@Tr*Pe-Ch-NPs exhibited excellent biocompatibility in J774.2 and decreased cell viability in DLD-1, HT-29, and MCF7 cell lines. More cell internalization was seen in HT-29 and MCF7 due to overexpression of the OCTN2 and ATB0,+ transporter (CE transporters) compared to DLD-1. The cell cycle profile, reactive oxygen species, apoptosis, and mitochondrial membrane potential assays were performed to explore the chemo-preventive mechanism of CE-IHP@Tr*Pe-Ch-NPs. Moreover, the in-silico docking studies revealed enhanced interactive behavior of CE-IHP@Tr*Pe-Ch-NPs, thereby proving their targeting ability. All the findings suggested that CE-IHP@Tr*Pe-Ch-NPs could be a promising drug delivery approach for colon cancer targeting.


Assuntos
Quitosana , Nanopartículas , Humanos , Ácido Fítico , Pectinas/farmacologia , Carnitina , Células MCF-7 , Colo , Portadores de Fármacos
11.
Arthrosc Sports Med Rehabil ; 6(1): 100862, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38304467

RESUMO

Purpose: To analyze epidemiology, mechanisms, and diagnoses of upper extremity volleyball injuries in youth who present to United States emergency departments. Methods: Data from the National Electronic Injury Surveillance System were analyzed for upper extremity volleyball injuries in patients ≤18 years old from January 1, 2012, to December 31, 2022. Data were collected for body part, diagnosis, mechanism of injury, and disposition. Weighted national estimates were calculated using the hospitals' corresponding statistical sample weights. Linear regressions were used to analyze annual trends. χ2 tests were used to analyze categorical variables. Results: A weighted national estimate of 131,624 upper extremity volleyball-related injuries occurred in the study period. Average age was 13.9 ± 2.3 years. Female patients constituted 77.6% of patients; 99.3% of patients did not require admission. The most common body parts injured were fingers (43.0%), wrists (22.8%), and shoulders (12.2%). The most common identifiable mechanisms of injury were impacts with the floor (19.4%), impacts with the ball (14.7%), and spikes/serves (5.7%). Most common diagnoses were strains/sprains (42.6%) and fractures (19.5%). Most common locations of fracture were fingers (57.4% of all fractures), wrists (16.6%), and lower arms (12.4%). There was a decrease of 544 overall injuries per year (P = .03, 95% confidence interval [CI] -1031 to -58). Female players experienced more contusions/abrasions (16.0% vs 9.9%, P < .001) and strains/sprains (46.1% vs 30.4%, P < .001) compared with male players. Female patients had decreases of 513 overall injuries (P = .01, 95% CI -881 to -144), 349 strains/sprains (P = .002, 95% CI -530 to -168), 102 contusions/abrasions (P = .008, 95% CI 170 to -34), and 92 fractures per year (P = .03, 95% CI -175 to -10). Conclusions: Youth volleyball players are at risk of upper extremity injury, particularly involving the fingers, wrist, and shoulder. Despite increasing national participation in youth volleyball, there is a decreasing incidence of upper extremity injuries. Level of Evidence: Level IV, prognostic case series.

12.
J Nat Prod ; 87(2): 424-438, 2024 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-38289177

RESUMO

Ever since the isolation of Amycolatopsis mediterranei in 1957, this strain has been the focus of research worldwide. In the last 60 years or more, our understanding of the taxonomy, development of cloning vectors and conjugation system, physiology, genetics, genomics, and biosynthetic pathway of rifamycin B production in A. mediterranei has substantially increased. In particular, the development of cloning vectors, transformation system, characterization of the rifamycin biosynthetic gene cluster, and the regulation of rifamycin B production by the pioneering work of Heinz Floss have made the rifamycin polyketide biosynthetic gene cluster (PKS) an attractive target for extensive genetic manipulations to produce rifamycin B analogues which could be effective against multi-drug-resistant tuberculosis. Additionally, a better understanding of the regulation of rifamycin B production and the application of newer genomics tools, including CRISPR-assisted genome editing systems, might prove useful to overcome the limitations associated with low production of rifamycin analogues.


Assuntos
Actinomycetales , Rifamicinas , Amycolatopsis , Vias Biossintéticas/genética , Rifamicinas/metabolismo
13.
J Fluoresc ; 34(1): 341-352, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37249676

RESUMO

Diversely substituted methoxy derivatives of arylpiperazinyl-alkyl benzothiazolone has been evaluated as specific probe for 5HT7. To determine the best methoxy derivative for 5HT7 receptor affinity, we synthesised a number of 2-benzothiazolone arylalkyl piperazine derivatives. In-vitro/vivo studies with C-2 substituted [11C]ABT showed 5HT7 specific binding. The radiochemical purity of [11C]ABT was found to be more than 99% with radiochemical stability persistence for more than 1.5 hr at 25 °C. The interaction of BSA and ABT has been analysed by photophysical studies for better understanding of properties such as adsortion, distribution, metabolism and elemination (ADME). The interaction between ABT and BSA was analyzed by using the UV-vis and fluorescence spectra. UV-vis spectra analyzed the changes in primary structure of BSA on its interaction with ABT. ABT showed quenched fluorescence emission intensity of tryptophan residues in BSA via static quenching mechanism. This study might help to understand how ABT binds to serum protein or subsequently to know the ADME of this drug candidate.


Assuntos
Serotonina , Soroalbumina Bovina , Soroalbumina Bovina/química , Serotonina/metabolismo , Espectrometria de Fluorescência , Dicroísmo Circular , Radiobiologia , Ligação Proteica , Termodinâmica
14.
Phytomedicine ; 123: 155181, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38091824

RESUMO

BACKGROUND: Triple negative breast cancer (TNBC) is the most aggressive subtype of breast cancer and exhibits high rate of chemoresistance, metastasis, and relapse. This can be attributed to the failure of conventional therapeutics to target a sub-population of slow cycling or quiescent cells called as cancer stem cells (CSCs). Therefore, elimination of CSCs is essential for effective TNBC treatment. PURPOSE: Research suggests that breast CSCs exhibit elevated glycolytic metabolism which directly contributes in maintenance of stemness, self-renewability and chemoresistance as well as in tumor progression. Therefore, this study aimed to target rewired metabolism which can serve as Achilles heel for CSCs population and have far reaching effect in TNBC treatment. METHODS: We used two preclinical models, zebrafish and nude mice to evaluate the fate of nanoparticles as well as the therapeutic efficacy of both piperlongumine (PL) and its nanomedicine (PL-NPs). RESULTS: In this context, we explored a phytochemical piperlongumine (PL) which has potent anti-cancer properties but poor pharmacokinetics impedes its clinical translation. So, we developed PLGA based nanomedicine for PL (PL-NPs), and demonstrated that it overcomes the pharmacokinetic limitations of PL, along with imparting advantages of selective tumor targeting through Enhanced Permeability and Retention (EPR) effect in zebrafish xenograft model. Further, we demonstrated that PL-NPs efficiently inhibit glycolysis in CSCs through inhibition of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) by modulating glutathione S-transferase pi 1 (GSTP1) and upregulation of fructose-1,6-bisphosphatase 1 (FBP1), a rate-limiting enzyme in gluconeogenesis. We also illustrated that inhibition of glycolysis results in overall tumor regression in two preclinical models. CONCLUSION: This study discusses novel mechanism of action by which PL acts on CSCSs. Taken together our study provides insight into development of PL based nanomedicine which could be exploited in clinics to achieve complete eradication of TNBC by targeting CSCs.


Assuntos
Benzodioxóis , Neoplasias de Mama Triplo Negativas , Animais , Camundongos , Humanos , Neoplasias de Mama Triplo Negativas/metabolismo , Peixe-Zebra/metabolismo , Nanomedicina , Camundongos Nus , Linhagem Celular Tumoral , Recidiva Local de Neoplasia/metabolismo , Células-Tronco Neoplásicas , Gliceraldeído-3-Fosfato Desidrogenases/metabolismo , Gliceraldeído-3-Fosfato Desidrogenases/farmacologia , Gliceraldeído-3-Fosfato Desidrogenases/uso terapêutico , Glicólise
15.
Phytother Res ; 38(2): 556-591, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37919622

RESUMO

Breast Cancer (BC) is the most prevalent type of cancer in the world. Current treatments include surgery, radiation, and chemotherapy but often are associated with high toxicity to normal tissues, chemoresistance, and relapse. Thus, developing novel therapies which could combat these limitations is essential for effective treatment. In this context, phytochemicals are increasingly getting popular due to their safety profile, ability to efficiently target tumors, and circumvent limitations of existing treatments. Essential Oils (EOs) are mixtures of various phytochemicals which have shown potential anticancer activity in preclinical BC models. However, their clinical translation is limited by factors such as high volatility, low stability, and poor solubility. Nanotechnology has facilitated their encapsulation in a variety of nanostructures and proven to overcome these limitations. In this review, we have efficiently summarized the current knowledge on the anticancer effect of EOs and constituents in both in in vitro and in in vivo BC models. Further, we also provide a descriptive account on the potential of nanotechnology in enhancing the anti-BC activity of EOs and their constituents. The papers discussed in this review were selected using the keywords "antiproliferative Essential Oils in breast cancer," "anticancer activity of Essential Oil in breast cancer," and "cytotoxicity of Essential Oils in breast cancer" performed in PubMed and ScienceDirect databases.


Assuntos
Neoplasias da Mama , Óleos Voláteis , Humanos , Feminino , Óleos Voláteis/farmacologia , Óleos Voláteis/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Recidiva Local de Neoplasia/tratamento farmacológico , Compostos Fitoquímicos/uso terapêutico
16.
Am J Clin Nutr ; 119(1): 174-184, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37931749

RESUMO

BACKGROUND: Eating a high-quality diet or adhering to a given dietary strategy may influence weight loss. However, these 2 factors have not been examined concurrently for those following macronutrient-limiting diets. OBJECTIVE: To determine whether improvement in dietary quality, change in dietary macronutrient composition, or the combination of these factors is associated with differential weight loss when following a healthy low-carbohydrate (HLC) or healthy low-fat (HLF) diet. DESIGN: Generally healthy adults were randomly assigned to HLC or HLF diets for 12 mo (n = 609) as part of a randomized controlled weight loss study. Participants with complete 24-h dietary recall data at baseline and 12-mo were included in this secondary analysis (total N = 448; N = 224 HLC, N = 224 HLF). Participants were divided into 4 subgroups according to 12-mo change in HEI-2010 score [above median = high quality (HQ) and below median = low quality (LQ)] and 12-mo change in macronutrient intake [below median = high adherence (HA) and above median = low adherence (LA) for net carbohydrate (g) or fat (g) for HLC and HLF, respectively]. Baseline to 12-mo changes in mean BMI were compared for those in HQ/HA, HQ/LA, LQ/HA subgroups with the LQ/LA subgroup within HLC and HLF. RESULTS: For HLC, changes (95 % confidence level [CI]) in mean BMI were -1.15 kg/m2 (-2.04, -0.26) for HQ/HA, -0.30 (-1.22, 0.61) for HQ/LA, and -0.80 (-1.74, 0.14) for LQ/HA compared with the LQ/LA subgroup. For HLF, changes (95% CI) in mean BMI were -1.11kg/m2 (-2.10, -0.11) for HQ/HA, -0.26 (-1.26, 0.75) for HQ/LA, and -0.66 (-1.74, 0.41) for LQ/HA compared with the LQ/LA subgroup. CONCLUSION: Within both HLC and HLF diet arms, 12-mo decrease in BMI was significantly greater in HQ/HA subgroups relative to LQ/LA subgroups. Neither HQ nor HA alone were significantly different than LQ/LA subgroups. Results of this analysis support the combination of dietary adherence and high-quality diets for weight loss. CLINICAL TRIAL REGISTRY: clinicaltrials.gov (Identifier: NCT01826591).


Assuntos
Dieta com Restrição de Gorduras , Dieta Redutora , Adulto , Humanos , Redução de Peso , Carboidratos
17.
Birth ; 51(1): 209-217, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37849421

RESUMO

BACKGROUND: Traumatic childbirth experiences are common in the United States - affecting a third to a fourth of mothers - with significant negative impacts on maternal health. Yet most research on traumatic childbirth focuses on white mothers' experiences. Drawing on a racially and ethnically diverse sample of mothers who experienced traumatic childbirth, this exploratory qualitative study examined Black, Latina, and Asian mothers' traumatic birth experiences and the role of obstetric racism in shaping these experiences. METHODS: In-depth, semi-structured interviews were conducted in 2019-2020 with 30 mothers who identified as women of color (37% Black, 40% Latina, and 23% Asian) who gave birth in the US and self-identified as having experienced a traumatic childbirth. Data were analyzed using qualitative content analysis. RESULTS: Mothers reported obstetric racism as core to their traumatic birth experiences. This racism manifested through practitioners' use of gendered and racialized stereotypes, denying and delegitimizing mothers' needs. Mothers shared key consequences of the obstetric racism they experienced, including postpartum anxiety and depression, increased medical mistrust, and decreased desire for future children. CONCLUSIONS: Mothers' reports suggest that obstetric racism played a role in their traumatic birth experiences. Particularly, practitioners' deployment of gendered and racialized stereotypes influenced mothers' treatment during birth. These findings point to opportunities to address obstetric racism during childbirth and improve patients' experiences through enhancing their agency and empowerment. The findings, in addition, highlight the need for increased practitioner training in anti-racist practice and cultural humility.


Assuntos
Parto , Racismo , Gravidez , Criança , Feminino , Humanos , Estados Unidos , Confiança , Parto Obstétrico , Mães , Pesquisa Qualitativa
18.
Biomater Adv ; 157: 213729, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38101068

RESUMO

Bioactive glasses have recently been attracted to meet the challenge in bone tissue regeneration, repair, healing, dental implants, etc. Among the conventional bio-glasses, a novel quaternary mesoporous nano bio-glass with composition 81S(81SiO2-(16-x)CaO-2P2O5-1Na2O-xMgO) (x = 0, 1.6, 2.4, 4 and 8 mol%) employing Stober's method has been explored for examining the above potential application through in-vitro SBF assay, MTT assay, antimicrobial activity and drug loading and release ability. With increasing the MgO concentration up to 4 mol%, from in-vitro SBF assay, we observe that HAp layer develops on the surface of the nBGs confirmed from XRD, FTIR and FESEM. MTT assay using MG-63 cells confirms the biocompatibility of the nBGs having cell viability >225 % for MGO_4 after 72 h which is more than the clinically used 45S5 bio-glass. We have observed cell viability of >125 % even after 168 h. Moreover, MGO_4 is found to restrict the growth of E. coli by 65 % while S. aureus by 75 %, confirming the antimicrobial activity. Despite an increase in the concentration of magnesium, nBGs are found to be non-toxic towards the RBCs up to 4 mol% of MgO while for 8 %, the hemolysis percentage is >6 % which is toxic. Being confirmed MGO_4 nBG as a bioactive material, various concentrations of drug (Dexamethasone (DEX)) loading and release kinetics are examined. We show that 80 % of loading in case of 10 mg-ml-1 and 70 % of cumulative release in 100 h. The mesoporous structure of MGO_4 having an average pore diameter of 5 nm and surface area of 216 m2 g-1 confirmed from BET supports the loading and release kinetics. We conclude that the quaternary MGO_4 nBG may be employed effectively for bone tissue regeneration due to its high biocompatibility, excellent in-vitro cell viability, antimicrobial response and protracted drug release.


Assuntos
Anti-Infecciosos , Óxido de Magnésio , Óxido de Magnésio/farmacologia , Óxido de Magnésio/química , Escherichia coli , Staphylococcus aureus , Anti-Infecciosos/farmacologia , Vidro/química
19.
J Acad Nutr Diet ; 2023 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-38081384

RESUMO

BACKGROUND: Most children in the United States consume low-quality diets. Identifying children's dietary patterns and their association with sociodemographic characteristics is important for designing tailored youth dietary interventions. OBJECTIVE: This study's objective was to use cluster analysis to investigate children's dietary patterns and these patterns' associations with sociodemographic characteristics. DESIGN: Data from two cycles (2015-2016 and 2017-2018) of the National Health and Nutrition Examination Survey were evaluated to examine dietary patterns. PARTICIPANTS AND SETTING: Participants included 3,044 US youth aged 2 to 11 years who completed at least 1 valid 24-hour diet recall. MAIN OUTCOME MEASURES: The main outcome measures were Healthy Eating Index (HEI) 2015 component and composite scores. STATISTICAL ANALYSES PERFORMED: A cluster analysis was performed on standardized scores of 11 components of the HEI-2015 to identify dietary patterns. One logistic analysis combined the two higher-HEI score clusters and the 2 lower-HEI score clusters to form a 3-category variable of higher-, medium-, and lower-HEI score clusters. Another logistic analysis contrasted 2 higher- and then the 2 lower-HEI clusters with each other to examine sociodemographic factors contributing to cluster membership. RESULTS: Five clusters were identified, each displaying a distinct dietary pattern. Older, non-Hispanic Black, and overweight children had higher odds of being in the higher-HEI clusters than the medium-HEI cluster. Being older and non-Hispanic Black were linked to higher odds of being in the lower-HEI clusters than the medium-HEI cluster. Conversely, being Mexican American and living with a college-educated reference person were associated with lower odds of being in the lower-HEI clusters compared with the medium-HEI cluster. Among the higher-HEI clusters, Mexican American and Asian American children had higher odds of being in the Pescatarian cluster. Among the lower-HEI clusters, children who were racially or ethnically minoritized had lower odds of being in the Excess Sugar cluster. CONCLUSIONS: Children in this study displayed different dietary patterns, with key sociodemographic variation.

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