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1.
Mol Cell Biochem ; 478(7): 1573-1598, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36434145

RESUMEN

Today, RNA aptamers are being considered promising theranostic tools against a wide variety of disorders. RNA aptamers can fold into complex shapes and bind to diverse nanostructures, macromolecules, cells, and viruses. It is possible to isolate RNA aptamers from a vast pool of nucleic acids via the Systematic Evolution of Ligands by Exponential Enrichment (SELEX) method. As therapeutics, aptamers have great potential because of their ability to bind to proteins and selectively limit their activities with negligible side effects. Several RNA aptamers with potential implications in cancer diagnosis are known to confer a great affinity for single-stranded DNA molecules, long non-coding RNAs, circulating tumor cells, vascular endothelial growth factors, and tissue and sera-derived exosomes in patients with different malignancies. Furthermore, clinical investigations have revealed the efficacy of RNA aptamer-based agents in imaging modalities. This review seeks to deliver new insights into the development, classification, nanomerization, and modification of RNA aptamers, as well as their applications in cancer theranostics. The aptamers' mechanism of action and their interest to clinical trials as theranostic agents are also discussed.


Asunto(s)
Aptámeros de Nucleótidos , Neoplasias , Humanos , Aptámeros de Nucleótidos/uso terapéutico , Aptámeros de Nucleótidos/química , Aptámeros de Nucleótidos/metabolismo , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Proteínas
2.
Saudi Pharm J ; 31(5): 669-677, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37181138

RESUMEN

Microneedle patches are promising transdermal drug delivery platforms with minimal invasiveness in a painless manner. Microneedle patch could be a promising alternate route for delivery of drugs having poor solubility and low bioavailability. This research work therefore, aimed to develop and characterize microneedle patch of thiolated chitosan (TCS) and polyvinyl acetate (PVA) for the systemic delivery of dydrogesterone (DYD). TCS-PVA-based microneedle patch was fabricated with 225 needles having a length of 575 µm with the sharp pointed end. Different ratios of TCS-PVA-based patch were employed to investigate the effects of mechanical tensile strength and percentage elongation. The scanning electron microscopy (SEM) revealed intact sharp-pointed needles. In vitro dissolution studies of microneedle patch (MN-P) were carried out by modified Franz-diffusion cell revealing the sustained release of DYD 81.45 ± 2.768 % at 48 hrs as compared to pure drug that showed 96.7 ± 1.75 % at 12 hrs. The transport of DYD (81%) across skin reaching the systemic circulation was evaluated through ex vivo permeation studies of MN-P. The skin penetration study through the parafilm M method showed good penetration with no deformation and breakage of needles along with no visible signs of skin irritation. Histological study of mice skins clearly showed the deeper penetration of needles into the skin. In summary, as-prepared MN-P show potential in developing an effective transdermal delivery system for DYD.

3.
Cell Biol Int ; 46(9): 1320-1344, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35830711

RESUMEN

Immune-mediated diseases (IMDs) are chronic conditions that have an immune-mediated etiology. Clinically, these diseases appear to be unrelated, but pathogenic pathways have been shown to connect them. While inflammation is a common occurrence in the body, it may either stimulate a favorable immune response to protect against harmful signals or cause illness by damaging cells and tissues. Nanomedicine has tremendous promise for regulating inflammation and treating IMIDs. Various nanoparticles coated with nanotherapeutics have been recently fabricated for effective targeted delivery to inflammatory tissues. RNA interference (RNAi) offers a tremendous genetic approach, particularly if traditional treatments are ineffective against IMDs. In cells, several signaling pathways can be suppressed by using RNAi, which blocks the expression of particular messenger RNAs. Using this molecular approach, the undesirable effects of anti-inflammatory medications can be reduced. Still, there are many problems with using short-interfering RNAs (siRNAs) to treat IMDs, including poor localization of the siRNAs in target tissues, unstable gene expression, and quick removal from the blood. Nanotherapeutics have been widely used in designing siRNA-based carriers because of the restricted therapy options for IMIDs. In this review, we have discussed recent trends in the fabrication of siRNA nanodelivery systems, including lipid-based siRNA nanocarriers, liposomes, and cationic lipids, stable nucleic acid-lipid particles, polymeric-based siRNA nanocarriers, polyethylenimine (PEI)-based nanosystems, chitosan-based nanoformulations, inorganic material-based siRNA nanocarriers, and hybrid-based delivery systems. We have also introduced novel siRNA-based nanocarriers to control IMIDs, such as pulmonary inflammation, psoriasis, inflammatory bowel disease, ulcerative colitis, rheumatoid arthritis, etc. This study will pave the way for new avenues of research into the diagnosis and treatment of IMDs.


Asunto(s)
Nanomedicina , Nanopartículas , Humanos , Inflamación/genética , Inflamación/terapia , Lípidos , Nanopartículas/uso terapéutico , Interferencia de ARN , ARN Interferente Pequeño/genética
4.
Pak J Pharm Sci ; 35(6(Special)): 1683-1690, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36861229

RESUMEN

Vancomycin (VAN) is an effective antibiotic due to its broad-spectrum bactericidal action. High performance liquid chromatography (HPLC), a powerful analytical technique is used for the in vitro/ in vivo quantification of VAN. The current study was aimed to detect the VAN from in vitro as well as the plasma after the extraction from blood of rabbits. The method was developed and validated according to International Council on Harmonization (ICH) Q2 R1 guidelines. Results showed that the peak of VAN was recorded at 2.96 and 2.57 min, respectively in vitro and serum. The coefficient of VAN turned out to be >0.9994 each for in vitro and in vivo samples. VAN was found linear in the range of 6.2-25000ng/mL. The values of accuracy and precision in terms of coefficient of variation (CV) were less than 2%, indicating the validity of the method. The values for LOD and LOQ were estimated to be 1.5 and 4.5ng/mL, correspondingly, which were lower than the values calculated from in vitro media. Furthermore, the score of the greenness found out to be 0.81, depicting good score using AGREE tool. It was concluded that the developed method was found accurate, precise, robust, rugged, linear, detectable and quantifiable at prepared analytical concentrations and could be used for in vitro and in vivo VAN determination.


Asunto(s)
Plasma , Vancomicina , Animales , Conejos , Cromatografía Líquida de Alta Presión , Antibacterianos
5.
Int J Mol Sci ; 22(6)2021 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-33803502

RESUMEN

Nanomaterials have received increasing attention due to their unique chemical and physical properties for the treatment of rheumatoid arthritis (RA), the most common complex multifactorial joint-associated autoimmune inflammatory disorder. RA is characterized by an inflammation of the synovium with increased production of proinflammatory cytokines (IL-1, IL-6, IL-8, and IL-10) and by the destruction of the articular cartilage and bone, and it is associated with the development of cardiovascular disorders such as heart attack and stroke. While a number of imaging tools allow for the monitoring and diagnosis of inflammatory arthritis, and despite ongoing work to enhance their sensitivity and precision, the proper assessment of RA remains difficult particularly in the early stages of the disease. Our goal here is to describe the benefits of applying various nanomaterials as next-generation RA imaging and detection tools using contrast agents and nanosensors and as improved drug delivery systems for the effective treatment of the disease.


Asunto(s)
Artritis Reumatoide/diagnóstico , Artritis Reumatoide/terapia , Inflamación/diagnóstico , Inflamación/terapia , Nanoestructuras/uso terapéutico , Nanomedicina Teranóstica , Animales , Antirreumáticos/uso terapéutico , Artritis Reumatoide/diagnóstico por imagen , Humanos , Inflamación/diagnóstico por imagen
6.
AAPS PharmSciTech ; 20(8): 325, 2019 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-31659563

RESUMEN

Localized intra-pocket, retentive, biodegradable, prolonged release thiolated membrane can provide an improved therapeutic efficacy of doxycycline at the site of action with evading off target side effects. To this end, thiolated chitosan-hyaluronic acid composite polymeric complex next-generation of the periodontal membrane was manufactured by solvent casting method. FTIR spectroscopic analysis displayed successful immobilization of thiol groups on the manufactured thiolated periodontal membrane. Moreover, XRD, DSC, AFM and TGA of the membrane confirmed the compatibility of ingredients and modifications in surface chemistry. The thiolated periodontal film was also investigated in terms of thickness, weight uniformity, water-uptake capacity, drug content, pH, entrapment efficiency, lysozymal degradation and release patterns. Also, mucoadhesion profile was explored on gingival mucosa. The immobilized thiol groups on thiolated chitosan and thiolated hyaluronate were found to be 168 ± 11 µM/g (mean ± SD, n = 3) and 189 ± 8 µM/g (mean ± SD, n = 3) respectively. Swelling capacity of the thiolated periodontal membrane was significantly ∼2-fold higher (p < 0.05) as compared to unmodified membrane. The obtained thiolated membrane depicted 3 -old higher mucoadhesive features as compared to the un-modified membrane. In vitro release kinetics indicated approximately more than 80% prolonged release within 7 days. Mechanical strength of the Thiolated bandage was also significantly ∼2-fold higher (p < 0.05) as compared to unmodified membrane. Ex-vivo retention study revealed enhanced retention of thiolated membrane as compared to unmodified membrane. In-vitro antimicrobial studies demonstrated that thiolated membrane could efficiently kill Porphyromonas gingivalis cells as compared to the native membrane. Moreover, ex-vivo biodegradation results indicated that 90% of the thiolated membrane was biodegradable in 28 days. Based on these findings, thiolated next-generation of the periodontal membrane seems to be promising for periodontitis therapy.


Asunto(s)
Antibacterianos/administración & dosificación , Doxiciclina/administración & dosificación , Sistemas de Liberación de Medicamentos/métodos , Bolsa Periodontal/tratamiento farmacológico , Compuestos de Sulfhidrilo/administración & dosificación , Adulto , Animales , Antibacterianos/metabolismo , Doxiciclina/química , Doxiciclina/metabolismo , Composición de Medicamentos , Evaluación Preclínica de Medicamentos/métodos , Cabras , Humanos , Bolsa Periodontal/metabolismo , Compuestos de Sulfhidrilo/química , Compuestos de Sulfhidrilo/metabolismo , Adulto Joven
7.
Pak J Med Sci ; 33(5): 1182-1187, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29142561

RESUMEN

OBJECTIVE: To evaluate and compare feto-maternal outcomes and glycemic control in metformin versus insulin treated gestational diabetics. METHODS: The study was conducted in 2010- 2012 as a part of M. Phil at Civil hospital, Lyari General Hospital and Mamji Hospital in Karachi. After written informed consent, 71 GDM diagnosed females with WHO criteria were enrolled. They were divided into two groups. Group-A, 32 females were given oral metformin 500 mg TDS while Group-B, 39 females were given insulin 0.8-0.9 mg/kg/day in two divided doses subcutaneously. Patients were followed till term. Feto-maternal outcomes were evaluated in 25 patients in each group who completed the study. RESULTS: When groups were compared, newborns in Group-B were significantly more in weight (p=0.01). Significant numbers of babies were delivered after 38 weeks of pregnancy in Group-B (P=0.021). There were two intrauterine deaths and significantly higher HbA1C at term in Group-B. (P=0.03). FBS at term was non-significant (p=0.079) and there was more number of cesarean sections due to feto-maternal disproportion in Group-B (28% vs.2%). Results analyzed for glycemic control before and after the treatment revealed that FBS was statistically less in Group-A (p=0.00) whereas for Group-B the value of FBS and HbA1C was statistically high. (p=0.002 & 0.04 respectively). CONCLUSION: Metformin has produced better effects on feto-maternal outcomes and glycemic control in comparison to Insulin in GDM.

8.
Pak J Med Sci ; 32(2): 480-4, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27182266

RESUMEN

OBJECTIVE: To find out the frequency of hypovitaminosis D and its associated risk factors in newly diagnosed pulmonary tuberculosis patients prior to administration of standard anti tuberculosis therapy. METHODS: This cross-sectional study was carried out in Ojha Institute of Chest Diseases-DUHS. After approval from BASR and following written informed consent eighty newly diagnosed, as per WHO criteria, tuberculosis patients were enrolled. Prior to the initiation of anti tuberculosis therapy, the serum vitamin D level was determined by 25-OH Vitamin D kit using the chemiluminescent immunoassay (CLIA) method. A cut off value of >30 ng/mL of serum vitamin D was taken as normal whereas a range between 10-30 ng/mL and <10 ng/mL were considered insufficient and deficient respectively. Frequency of socio-demographic associated risk factors of hypovitaminosis D was also determined. RESULTS: Out of eighty newly diagnosed tuberculosis patients 33 (41.25%) were males and 47(58.75%) were females with their ages ranging from 18-50 years. 54 patients (26 male and 28 female patients) were smokers. BMI of all the patients was found to be less than the normal ranges. Hypovitaminosis was present in all the cases. Vitamin D insufficiency was found in 49 participants (20 male and 29 female) whereas 31 patients (13 male and 18 female) were found to be vitamin D deficient. CONCLUSION: Prevalence of serum vitamin D level derangement is very high in newly diagnosed patients with pulmonary tuberculosis in our local setting which necessitates administration of adjuvant vitamin D along with standard anti tuberculosis therapy.

9.
Pak J Med Sci ; 32(6): 1522-1527, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-28083057

RESUMEN

OBJECTIVE: To evaluate the effects of diet control and Metformin on placental morphology in gestational diabetes mellitus (GDM). METHODS: After written informed consent 62 GDMs were enrolled. According to WHO criteria, 30 cases of GDMs with blood sugar level <130 mg/dl, were assigned Group B (2000-2500Kcal/day and 30 minute walk thrice weekly were kept on diet control and 32 cases of GDM with blood sugar level >130 mg/dl, assigned Group C were kept on diet with tablet Metformin,(500mg TDS) Finally 25 normal pregnant females were kept in Group A as control. After delivery placentae were preserved and evaluated for morphology. RESULTS: Heavy placentae with abundant villous immaturity, chorangiosis and syncytial knots in group B and fibrinoid necrosis and calcification in group C were seen. In group B versus A placental and cord width while in Group C versus A only cord width in gross morphology showed significant results. In group B versus A villous immaturity, chorangiosis, infarction and syncytial knots in light microscopy were present; similarly in B versus C placental width, chorangiosis and syncytial knots showed significant results, while in C versus A results were non-significant. CONCLUSION: Metformin produced beneficial effects on placental morphology being comparable to normal control in contrast to diet group.

10.
Pak J Med Sci ; 31(2): 355-9, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26101490

RESUMEN

OBJECTIVE: To determine correlation of serum total testosterone with body mass index (BMI) and waist hip ratio (WHR) in healthy adult males. METHODS: A cross sectional study was conducted on 200 nonsmoker healthy males (aged 30-50 years) university employees. They were selected by convenience sampling technique after a detailed medical history and clinical examination including BMI and Waist Hip Ratio (WHR) calculation. Blood sampling was carried out to measure serum total testosterone (TT) using facilities of Chemiluminescence assay (CLIA) technique in Dow Chemical Laboratory. Independent sample T test was used for mean comparisons of BMI and WHR in between low and normal testosterone groups. (Subjects having < 9.7 nmol/L of total testosterone in blood were placed in low testosterone group and subjects having ≥ 9.7 nmol/L of total testosterone in blood were placed in normal testosterone group). Correlation of testosterone with BMI and WHR was analyzed by Pearson Correlation. RESULTS: Mean (± SD) age of the subjects included in this study was 38.7 (± 6.563) years mean (± SD) total testosterone was 15.92 (±6.322)nmol/L. The mean (± SD) BMI, and WHR were 24.95 (±3.828) kg/m(2) and 0.946 (±0.0474) respectively. Statistically significant differences were observed in the mean values of BMI and WHR for the two groups of testosterone. Significant inverse correlation of serum total testosterone with BMI(r = -0.311, p = 0.000) was recorded in this study. However testosterone was not significantly correlated with waist/hip ratio.(r = -0.126, p = 0.076). CONCLUSION: Middle age men working at DUHS who have low level of serum total testosterone are more obese than individuals with normal total testosterone level.

11.
Pak J Med Sci ; 30(2): 240-4, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24772119

RESUMEN

OBJECTIVE: To observe the effects of exogenous insulin on placental, fetal and maternal outcomes in Gestational Diabetes Mellitus (GDM). METHODS: After screening and diagnoses(WHO criteria) 30 GDM patients(Group A) were kept on diet control and 39 GDM (Group B) who did not achieve glycemic targets were added subcutaneous insulin. Term placental weight, size, shape, consistency, fibrinoid necrosis, hemorrhages, cord color, length of the cord, completeness of membranes, weight and condition of baby and mode of delivery were assessed in 25 patients in each group. RESULT: Placental weight, cord width and baby weight were found to be more in Group B, than Group A and were statistically significant with p value 0.005, 0.02 and 0.003 respectively. Ten patients in group A and 17 patients in group B had cesarean deliveries. CONCLUSION: Exogenous insulin produces significant effects on the placental, fetal and maternal outcomes in patients with GDM.

12.
Acta Psychol (Amst) ; 247: 104303, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38797024

RESUMEN

Th is study offers empirical insights into investor behavior and its correlation with various behavioral biases in the context of investment decisions in the Pakistan Stock Exchange (PSX). Data was collected through a structured questionnaire from 261 individual investors in Pakistan. The study employs hierarchical regression analysis to test the hypothesis. It considers several behavioral biases, and statistically, anchoring and adjustment, overconfidence, and herding show a significant impact. The study uses financial literacy to examine its moderating effects on these biases, and the result suggests that it significantly influences behavioral biases related to investment decisions. The results underscore the unique investment behaviors in emerging markets, contrasting with established norms in well-developed financial markets. These findings can inform policymakers and stock market authorities about investor decision-making in emerging economies.


Asunto(s)
Toma de Decisiones , Inversiones en Salud , Humanos , Pakistán , Toma de Decisiones/fisiología , Adulto , Masculino , Femenino , Encuestas y Cuestionarios , Persona de Mediana Edad , Alfabetización , Adulto Joven
13.
Biosens Bioelectron ; 260: 116425, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-38824703

RESUMEN

Cancer antigen 15-3 (CA 15-3) is a crucial marker used in the diagnosis and monitoring of breast cancer (BC). The demand for early and precise cancer detection has grown, making the creation of biosensors that are highly sensitive and specific essential. This review paper provides a thorough examination of the progress made in optical and electrochemical biosensors for detecting the cancer biomarker CA 15-3. We focus on explaining their fundamental principles, sensitivity, specificity, and potential for point-of-care applications. The performance attributes of these biosensors are assessed by considering their limits of detection, reaction times, and operational stability, while also making comparisons to conventional methods of CA 15-3 detection. In addition, we explore the incorporation of nanomaterials and innovative transducer components to improve the performance of biosensors. This paper conducts a thorough examination of recent studies to identify the existing obstacles. It also suggests potential areas for future research in this fast progressing field.The paper provides insights into their advancement and utilization to enhance patient outcomes. Both categories of biosensors provide significant promise for the detection of CA 15-3 and offer distinct advantages compared to conventional analytical approaches.


Asunto(s)
Biomarcadores de Tumor , Técnicas Biosensibles , Neoplasias de la Mama , Técnicas Electroquímicas , Mucina-1 , Humanos , Neoplasias de la Mama/diagnóstico , Técnicas Biosensibles/instrumentación , Técnicas Biosensibles/métodos , Femenino , Técnicas Electroquímicas/métodos , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/sangre , Mucina-1/análisis
14.
Clin Case Rep ; 12(6): e8969, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38827939

RESUMEN

Key Clinical Message: The case highlights the importance of decisive action in addressing large gallstones causing gastric outlet obstruction. The chosen single-stage surgical approach reflects the need to manage both obstruction and the gallstone simultaneously. Abstract: Bouveret's syndrome is a rare cause of gastric outlet obstruction secondary to gallstones entering the enteric system through an acquired cholecystoduodenal fistula. Here, we present the case of an 85-year-old female who presented to our emergency department with gastric outlet obstruction secondary to a large gallstone in the third part of the duodenum. Abdominal X-ray did not demonstrate air-fluid levels but revealed a dilated gastric shadow, suggesting gastric outlet obstruction. EGD showed a dilated stomach and a hard, golf ball-sized gallstone in the duodenum. CT scan showed a distended stomach with a large gallstone obstructing the DJ junction and air in the biliary tree. Findings were suggestive of perforation of the gallbladder with stone impaction in the duodenojejunal (DJ) junction. The patient was managed surgically with a one-stage procedure comprising enterotomy, fistula closure, and cholecystectomy. Although Bouveret's syndrome is rare, it is important for practicing surgeons to have a high index of suspicion for this condition due to the high mortality associated with it.

16.
Eur J Med Chem ; 259: 115676, 2023 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-37499287

RESUMEN

Etoposide (ETO), a popular anticancer drug that inhibits topoisomerase II enzymes, may be administered more effectively and efficiently due to nanomedicine. The therapeutic application of ETO is constrained by its limited solubility, weak absorption, and severe side effects. This article summarizes substantial progress made in the development of ETO nanomedicine for the treatment of cancer. It discusses various organic and inorganic nanostructures used to load or affix ETOs, such as lipids, liposomes, polymeric nanoparticles (NPs), dendrimers, micelles, gold NPs, iron oxide NPs, and silica NPs. In addition, it evaluates the structural properties of these nanostructures, such as their size, zeta potential, encapsulation efficiency, and drug release mechanism, as well as their in vitro or in vivo performance. The article also emphasizes the co-delivery of ETO with other medications or agents to produce synergistic effects or combat drug resistance in the treatment of cancer. It concludes with a discussion of the challenges and potential avenues for clinical translation of ETO nanomedicine.


Asunto(s)
Antineoplásicos , Nanopartículas , Neoplasias , Humanos , Etopósido/farmacología , Etopósido/uso terapéutico , Nanomedicina , Antineoplásicos/química , Liposomas/química , Neoplasias/tratamiento farmacológico , Sistemas de Liberación de Medicamentos , Portadores de Fármacos/química , Nanopartículas/química
17.
Am J Transl Res ; 15(5): 3115-3130, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37303662

RESUMEN

OBJECTIVE: The SEC24D (SEC24 Homolog D, COPII Coat Complex Component) gene belongs to the SEC24 subfamily of genes. The protein encoded by this gene, along with its other binding partners, mediates the transport of newly-synthesized proteins from the endoplasmic reticulum to the Golgi apparatus. METHODS: A pan-cancer analysis of this gene, as well as its diagnostic and prognostic implications, are lacking in the medical literature. First, we analyzed SEC24D gene expression, its prognostic effect, promoter methylation level, genetic alteration landscape, pathways, CD8+ T immune cell infiltration, and gene-drug network in various types of cancer through various online databases and bioinformatic tools. Then, we performed the expression and methylation validation analysis of the SEC24D gene on cell lines using RNA sequencing (RNA-seq) and targeted bisulfite sequencing (bisulfite-seq) techniques. RESULTS: Bioinformatic analysis showed that the SEC24D gene was overexpressed in metastasis across Kidney Renal Clear Cell Carcinoma (KIRC), Lung Squamous Cell Carcinoma (LUSC), and Stomach Adenocarcinoma (STAD) patients and was a prognostic risk factor. Then, using RNA sequencing and targeted bisulfite sequencing analysis, it was validated in cell lines that SEC24D was overexpressed and hypomethylated in KIRC patients. Mutational analysis revealed that SEC24D was mutated less frequently in KIRC, LUSC, and STAD patients. It was further observed that CD8+ T cell infiltration levels were increased in SEC24D-overexpressed KIRC, LUSC, and STAD samples. Pathway enrichment analysis of SEC24D-associated genes revealed their participation in two important pathways. Moreover, we suggested a few valuable drugs for treating KIRC, LUSC, and STAD patients with respect to overexpressed SEC24D. CONCLUSION: This is the first pan-cancer study that details the oncogenic roles of SEC24D among different cancers.

18.
Int J Biol Macromol ; 242(Pt 1): 124741, 2023 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-37156311

RESUMEN

Salmonella Typhi is an intracellular bacterium causing a variety of enteric diseases, being typhoid fever the most common. Current modalities for treating S. typhi infection are subjected to multi-drug resistance. Herein, a novel macrophage targeting approach was developed via coating bioinspired mannosylated preactivated hyaluronic acid (Man-PTHA) ligands on a self-nanoemulsifying drug delivery system (SNEDDS) loaded with the anti-bacterial drug ciprofloxacin (CIP). The shake flask method was used to determine the drug solubility in the different excipients (oil, surfactants and co-surfactants). Man-PTHA were characterized by physicochemical, in vitro, and in vivo parameters. The mean droplet size was 257 nm, with a PDI of 0.37 and zeta potential of -15 mV. In 72 h, 85 % of the drug was released in a sustained manner, and the entrapment efficiency was 95 %. Outstanding biocompatibility, mucoadhesion, muco-penetration, anti-bacterial action and hemocompatibility were observed. Intra-macrophage survival of S. typhi was minimal (1 %) with maximum nanoparticle uptake, as shown by their higher fluorescence intensity. Serum biochemistry evaluation showed no significant changes or toxicity, and histopathological evaluation confirmed the entero-protective nature of the bioinspired polymers. Overall, results confirm that Man-PTHA SNEDDS can be employed as novel and effective delivery systems for the therapeutic management of S. typhi infection.


Asunto(s)
Infecciones Bacterianas , Nanopartículas , Nanoestructuras , Humanos , Masculino , Ácido Hialurónico , Emulsiones/química , Sistemas de Liberación de Medicamentos/métodos , Nanoestructuras/química , Tensoactivos/química , Solubilidad , Nanopartículas/química , Tamaño de la Partícula , Administración Oral
19.
Drug Discov Today ; 28(9): 103673, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37331691

RESUMEN

Chronic wounds are ubiquitously inhabited by bacteria, and they remain a challenge as they cause significant discomfort and because their treatment consumes huge clinical resources. To reduce the burden that chronic wounds place upon both patients and health services, a wide variety of approaches have been devised and investigated. Bioinspired nanomaterials have shown great success in wound healing when compared to existing approaches, showing better ability to mimic natural extracellular matrix (ECM) components and thus to promote cell adhesion, proliferation, and differentiation. Wound dressings that are based on bioinspired nanomaterials can be engineered to promote anti-inflammatory mechanisms and to inhibit the formation of microbial biofilms. We consider the extensive potential of bioinspired nanomaterials in wound healing, revealing a scope beyond that covered previously.


Asunto(s)
Antiinfecciosos , Nanoestructuras , Humanos , Cicatrización de Heridas , Antiinfecciosos/farmacología , Antiinfecciosos/uso terapéutico
20.
Gels ; 9(10)2023 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-37888404

RESUMEN

BACKGROUND: Dermatitis is skin disorder that is complicated by recurrent infections of skin by bacteria, viruses, and fungi. Spilanthol is an active constituent of Spilanthes acmella, which possess strong anti-bacterial properties. The purpose of this study was to develop a herbal emulgel for the treatment of dermal bacterial infections, as microscopic organisms have created solid resistance against anti-microbials. METHODS: Emulgels were prepared and characterized for parameters such as physical examination, rheological studies, spreading coefficient, bio-adhesive strength measurement, extrudability study, antibacterial activity, FTIR analysis, in vitro drug dissolution, and ex vivo permeation studies. RESULT: With a statistically significant p-value = 0.024, 100% antibacterial activity was observed by F4 against Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli (mean ± S.D) (25.33 ± 0.28, 27.33 ± 0.5, and 27 ± 0.5). However, maximum antibacterial effect 100% formulations produced zones of inhibitions against E. colip-value = 0.001. The mean zone of inhibition produced by F4 was greatest among all at 26.44 ± 0.37 mm (mean ± S.D). The F4 formulation produced a maximum percentage dissolution, permeation, and flux of 86.35 ± 0.576, 55.29 ± 0.127%, and 0.5532 ug/cm2/min, respectively. CONCLUSIONS: The present study therefore, suggests the use of S. acmella extract and olive oil containing emulgel for treating bacterial skin infections.

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