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2.
Proc Natl Acad Sci U S A ; 121(11): e2307802121, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38437557

RESUMO

RNA interference (RNAi) therapeutics are an emerging class of medicines that selectively target mRNA transcripts to silence protein production and combat disease. Despite the recent progress, a generalizable approach for monitoring the efficacy of RNAi therapeutics without invasive biopsy remains a challenge. Here, we describe the development of a self-reporting, theranostic nanoparticle that delivers siRNA to silence a protein that drives cancer progression while also monitoring the functional activity of its downstream targets. Our therapeutic target is the transcription factor SMARCE1, which was previously identified as a key driver of invasion in early-stage breast cancer. Using a doxycycline-inducible shRNA knockdown in OVCAR8 ovarian cancer cells both in vitro and in vivo, we demonstrate that SMARCE1 is a master regulator of genes encoding proinvasive proteases in a model of human ovarian cancer. We additionally map the peptide cleavage profiles of SMARCE1-regulated proteases so as to design a readout for downstream enzymatic activity. To demonstrate the therapeutic and diagnostic potential of our approach, we engineered self-assembled layer-by-layer nanoparticles that can encapsulate nucleic acid cargo and be decorated with peptide substrates that release a urinary reporter upon exposure to SMARCE1-related proteases. In an orthotopic ovarian cancer xenograft model, theranostic nanoparticles were able to knockdown SMARCE1 which was in turn reported through a reduction in protease-activated urinary reporters. These LBL nanoparticles both silence gene products by delivering siRNA and noninvasively report on downstream target activity by delivering synthetic biomarkers to sites of disease, enabling dose-finding studies as well as longitudinal assessments of efficacy.


Assuntos
Neoplasias Ovarianas , Peptídeos , Humanos , Feminino , Interferência de RNA , Peptídeos/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/terapia , Peptídeo Hidrolases , RNA Interferente Pequeno/genética , Endopeptidases , Proteínas Cromossômicas não Histona , Proteínas de Ligação a DNA
3.
Appl Biochem Biotechnol ; 196(2): 1008-1043, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37314636

RESUMO

Over the last few decades, the application of nanoparticles (NPs) gained immense attention towards environmental and biomedical applications. NPs are ultra-small particles having size ranges from 1 to 100 nm. NPs loaded with therapeutic or imaging compounds have proved a versatile approach towards healthcare improvements. Among various inorganic NPs, zinc ferrite (ZnFe2O4) NPs are considered as non-toxic and having an improved drug delivery characteristics . Several studies have reported broader applications of ZnFe2O4 NPs for treating carcinoma and various infectious diseases. Additionally, these NPs are beneficial for reducing organic and inorganic environmental pollutants. This review discusses about various methods to fabricate ZnFe2O4 NPs and their physicochemical properties. Further, their biomedical and environmental applications have also been explored comprehensively.


Assuntos
Nanopartículas , Zinco , Nanopartículas/química , Compostos Férricos/química , Sistemas de Liberação de Medicamentos
4.
Appl Biochem Biotechnol ; 196(2): 1058-1078, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37318689

RESUMO

Metal/Metal Oxide nanoparticles (M/MO NPs) exhibit potential biomedical applications due to their tunable physicochemical properties. Recently, the biogenic synthesis of M/MO NPs has gained massive attention due to their economical and eco-friendly nature. In the present study, Nyctanthes arbor-tristis (Nat) flower extract-derived Zinc Ferrite NPs (Nat-ZnFe2O4 NPs) were synthesized and physicochemically characterized by FTIR, XRD, FE-SEM, DLS, and other instruments to study their crystallinity, size, shape, net charge, presence of phytocompounds on NP's surface and several other features. The average particle size of Nat-ZnFe2O4 NPs was approx. 25.87 ± 5.67 nm. XRD results showed the crystalline nature of Nat-ZnFe2O4 NPs. The net surface charge on NPs was -13.28 ± 7.18 mV. When tested on mouse fibroblasts and human RBCs, these NPs were biocompatible and hemocompatible. Later, these Nat-ZnFe2O4 NPs exhibited potent anti-neoplastic activity against pancreatic, lung, and cervical cancer cells. In addition, NPs induced apoptosis in tested cancer cells through ROS generation. These in vitro studies confirmed that Nat-ZnFe2O4 NPs could be used for cancer therapy. Moreover, further studies are recommended on ex vivo platforms for future clinical applications.


Assuntos
Nanopartículas Metálicas , Nanopartículas , Neoplasias , Óxido de Zinco , Animais , Camundongos , Humanos , Nanopartículas/química , Nanopartículas Metálicas/química , Zinco , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Óxidos , Neoplasias/tratamento farmacológico , Antibacterianos/farmacologia , Óxido de Zinco/química
5.
Appl Biochem Biotechnol ; 196(1): 382-399, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37133677

RESUMO

Inorganic nanoparticles (NPs) have played an important role as nano-drug delivery systems during cancer therapy in recent years. These NPs can carry cancer therapeutic agents. Due to this, they are considered a promising ancillary to traditional cancer therapies. Among inorganic NPs, Zinc Oxide (ZnO) NPs have been extensively utilized in cellular imaging, gene/drug delivery, anti-microbial, and anti-cancerous applications. In this study, a rapid and cost-effective method was used to synthesize Nat-ZnO NPs using the floral extract of the Nyctanthes arbor-tristis (Nat) plant. Nat-ZnO NPs were physicochemically characterized and tested further on in vitro cancer models. The average hydrodynamic diameter (Zaverage) and the net surface charge of Nat-ZnO NPs were 372.5 ± 70.38 d.nm and -7.03 ± 0.55 mV, respectively. Nat-ZnO NPs exhibited a crystalline nature. HR-TEM analysis showed the triangular shape of NPs. Furthermore, Nat-ZnO NPs were also found to be biocompatible and hemocompatible when tested on mouse fibroblast cells and RBCs. Later, the anti-cancer activity of Nat-ZnO NPs was tested on lung and cervical cancer cells. These NPs displayed potent anti-cancer activity and induced programmed cell death in cancer cells.


Assuntos
Nanopartículas Metálicas , Nanopartículas , Óxido de Zinco , Animais , Camundongos , Óxido de Zinco/farmacologia , Óxido de Zinco/química , Antibacterianos/farmacologia , Nanopartículas Metálicas/química , Testes de Sensibilidade Microbiana , Flores , Extratos Vegetais/farmacologia , Extratos Vegetais/química
6.
Chin J Traumatol ; 2023 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-37838577

RESUMO

PURPOSE: Renal trauma constitutes 0.5% - 5% of all trauma patients, and 10% - 20% of abdominal trauma. It is the most commonly injured organ in the genitourinary tract. Road traffic crash (RTC) is the most common cause. In recent years due to the advances in radiological imaging and endovascular techniques, there has been an increase in the nonoperative management of renal trauma. We investigated a large trauma cohort at a level I trauma centre to evaluate patients' demographics with renal trauma, their management, and the outcomes. METHODS: This was a retrospective analysis of the prospectively collected data of renal trauma patients managed from January 2016 to December 2020. Patients who visited the level I trauma centre in north India with renal trauma were included in this study. Patients who were dead on arrival in the emergency department were excluded. Demographics, mechanism of injury, presence of hemorrhagic shock, associated injuries, complications, length of hospital stay (LOS), discharge, and mortality were recorded. The data were entered in Microsoft Excel 365 and analysed using SPSS version 21. RESULTS: This study collected data from 303 renal trauma patients. Males constituted 86.5% of the patients. Most patients were young, aged from 20 - 40 years. Blunt renal trauma was the predominant mode of injury (n = 270, 89.1%). RTCs (n = 190, 62.7%) and falls from height (n = 65, 21.4%) were the 2 most common mechanisms of injury. Focused assessment with sonography in trauma was positive in 68.4% of patients. Grade III (grading by the American Association for the Surgery of Trauma) renal trauma (30.4%) was the most common grade in our study. The liver (n = 104, 34.3%) and splenic trauma (n = 96, 31.7%) were the most commonly associated injuries. Of the 303 patients, 260 (85.8%) were managed nonoperatively. The mean (SD) of the patients' LOS was 12.5 (6.5) days. There were 25 (8.3%) mortalities during the study period and all of them had associated other injuries. The comparison of LOS of isolated renal trauma group and renal trauma with associated injuries group was not statistically significant (p = 0.322). All the patients who died during the study period had renal trauma with associated other organ injuries. None of the patients with isolated renal trauma died during the study. The outcome comparison between both groups was not statistically significant (p = 0.110). CONCLUSION: Renal trauma predominantly occurs in young males, especially due to RTCs followed by fall from height. Focused assessment with sonography in trauma is not reliable in detecting renal injuries, other diagnostic tools such as contrast enhanced computed tomography torso should be considered in diagnosing and grading these injuries. Renal trauma usually does not occur in isolation. Majority are associated with other abdominal and extra abdominal injuries. Most of the times these injuries can be managed nonoperatively, which can achieve a low mortality. The patients who required surgery had high mortality as compared to patients who managed nonoperatively. These patients who required surgery had either severe renal or extra renal trauma and were in hemorrhagic shock. Renal trauma from this large cohort may contribute to improving the quality of care for patients with renal trauma by obtaining knowledge about the patient's characteristics, management, and outcomes.

7.
Clin Cancer Res ; 29(20): 4306-4313, 2023 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-37566241

RESUMO

PURPOSE: Human papillomavirus (HPV) is causally linked to oropharyngeal squamous cell carcinoma (OPSCC). Consensus guidelines recommend clinical exams and imaging in decreasing frequency as part of posttreatment surveillance for recurrence. Plasma tumor tissue modified viral (TTMV)-HPV DNA testing has emerged as a biomarker which can inform disease status during surveillance. EXPERIMENTAL DESIGN: This retrospective observational cohort study involved 543 patients who completed curative-intent therapy for HPV-associated OPSCC between February 2020 and January 2022 at eight U.S. cancer care institutions. We determined the negative predictive value (NPV) of TTMV-HPV DNA for recurrence when matched to physician-reported clinical outcome data (median follow-up time: 27.9 months; range: 4.5-154). RESULTS: The cohort included mostly men with a median age of 61 who had locoregionally advanced disease. HPV status was determined by p16 positivity in 87% of patients, with a positive HPV PCR/ISH among 55%; while pretreatment TTMV-HPV DNA status was unknown for most (79%) patients. Patients had a mean of 2.6 tests and almost half had three or more TTMV-HPV DNA results during surveillance. The per-test and per-patient sensitivity of the assay was 92.5% [95% confidence interval (CI): 87.5-97.5] and 87.3% (95% CI: 79.1-95.5), respectively. The NPV for the assay was 99.4% (95% CI: 98.9-99.8) and 98.4% (95% CI: 97.3-99.5), respectively. CONCLUSIONS: TTMV-HPV DNA surveillance testing yields few false negative results and few missed recurrences. These data could inform decisions on when to pursue reimaging following first disease restaging and could inform future surveillance practice. Additional study of how pretreatment TTMV-HPV DNA status impacts sensitivity for recurrence is needed.

8.
Mol Pharm ; 20(8): 3698-3740, 2023 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-37486263

RESUMO

Human viral oncogenesis is a complex phenomenon and a major contributor to the global cancer burden. Several recent findings revealed cellular and molecular pathways that promote the development and initiation of malignancy when viruses cause an infection. Even, antiviral treatment has become an approach to eliminate the viral infections and prevent the activation of oncogenesis. Therefore, for a better understanding, the molecular pathogenesis of various oncogenic viruses like, hepatitis virus, human immunodeficiency viral (HIV), human papillomavirus (HPV), herpes simplex virus (HSV), and Epstein-Barr virus (EBV), could be explored, especially, to expand many potent antivirals that may escalate the apoptosis of infected malignant cells while sparing normal and healthy ones. Moreover, contemporary therapies, such as engineered antibodies antiviral agents targeting signaling pathways and cell biomarkers, could inhibit viral oncogenesis. This review elaborates the recent advancements in both natural and synthetic antivirals to control viral oncogenesis. The study also highlights the challenges and future perspectives of using antivirals in viral oncogenesis.


Assuntos
Infecções por Vírus Epstein-Barr , Neoplasias , Humanos , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Herpesvirus Humano 4 , Carcinogênese , Neoplasias/tratamento farmacológico , Neoplasias/prevenção & controle , Neoplasias/patologia , Antivirais/farmacologia , Antivirais/uso terapêutico
9.
Am J Surg ; 226(4): 477-484, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37349222

RESUMO

BACKGROUND: Adequate lymph node (LN) excision is imperative for pathologic staging and determination of adjuvant treatment. METHODS: he 2004-2017 National Cancer Database (NCDB) was queried for curative colon cancer resections. Tumors were categorized by location: left, right, and transverse colon cancers. Adequate (12-20 LNs) vs. inadequate (<12 LNs) lymphadenectomy was examined and sub-analysis of <12 LNs, 12-20 LNs or >20 LNs. Primary outcome was predictors of inadequate lymph node retrieval. RESULTS: Of 101,551 patients, 11.2% (11,439) had inadequate lymphadenectomy. The inadequate lymphadenectomy rate steadily decreased. On multivariable analysis, inadequate LN retrieval was associated with transverse (OR 1.49, CI [1.30-1.71]) and left colon cancers (OR 2.66, CI [2.42-2.93], whereas income >$63,333 had decreased likelihood of inadequate LN retrieval (OR 0.68, CI[0.56-0.82]. CONCLUSION: We are making the grade as NCDB data demonstrates a steady decrease in inadequate lymphadenectomy (2004-2017). There remain socioeconomic risk factors for inadequate lymphadenectomy that need to be addressed.


Assuntos
Neoplasias do Colo , Linfoma , Masculino , Humanos , Prognóstico , Estadiamento de Neoplasias , Linfonodos/cirurgia , Linfonodos/patologia , Excisão de Linfonodo , Neoplasias do Colo/cirurgia , Neoplasias do Colo/patologia , Linfoma/cirurgia , Estudos Retrospectivos
10.
Diagnostics (Basel) ; 13(4)2023 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-36832208

RESUMO

The NavDx® blood test analyzes tumor tissue modified viral (TTMV)-HPV DNA to provide a reliable means of detecting and monitoring HPV-driven cancers. The test has been clinically validated in a large number of independent studies and has been integrated into clinical practice by over 1000 healthcare providers at over 400 medical sites in the US. This Clinical Laboratory Improvement Amendments (CLIA), high complexity laboratory developed test, has also been accredited by the College of American Pathologists (CAP) and the New York State Department of Health. Here, we report a detailed analytical validation of the NavDx assay, including sample stability, specificity as measured by limits of blank (LOBs), and sensitivity illustrated via limits of detection and quantitation (LODs and LOQs). LOBs were 0-0.32 copies/µL, LODs were 0-1.10 copies/µL, and LOQs were <1.20-4.11 copies/µL, demonstrating the high sensitivity and specificity of data provided by NavDx. In-depth evaluations including accuracy and intra- and inter-assay precision studies were shown to be well within acceptable ranges. Regression analysis revealed a high degree of correlation between expected and effective concentrations, demonstrating excellent linearity (R2 = 1) across a broad range of analyte concentrations. These results demonstrate that NavDx accurately and reproducibly detects circulating TTMV-HPV DNA, which has been shown to aid in the diagnosis and surveillance of HPV-driven cancers.

11.
Oncol Res ; 32(1): 19-47, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38188681

RESUMO

Cancer is a leading cause of death globally, with limited treatment options and several limitations. Chemotherapeutic agents often result in toxicity which long-term conventional treatment. Phytochemicals are natural constituents that are more effective in treating various diseases with less toxicity than the chemotherapeutic agents providing alternative therapeutic approaches to minimize the resistance. These phytoconstituents act in several ways and deliver optimum effectiveness against cancer. Nevertheless, the effectiveness of phyto-formulations in the management of cancers may be constrained due to challenges related to inadequate solubility, bioavailability, and stability. Nanotechnology presents a promising avenue for transforming current cancer treatment methods through the incorporation of phytochemicals into nanosystems, which possess a range of advantageous characteristics such as biocompatibility, targeted and sustained release capabilities, and enhanced protective effects. This holds significant potential for future advancements in cancer management. Herein, this review aims to provide intensive literature on diverse nanocarriers, highlighting their applications as cargos for phytocompounds in cancer. Moreover, it offers an overview of the current advancements in the respective field, emphasizing the characteristics that contribute to favourable outcomes in both in vitro and in vivo settings. Lastly, clinical development and regulatory concerns are also discussed to check on the transformation of the concept as a promising strategy for combination therapy of phytochemicals and chemotherapeutics that could lead to cancer management in the future.


Assuntos
Neoplasias , Humanos , Terapia Combinada , Neoplasias/tratamento farmacológico
12.
Indian J Gastroenterol ; 41(6): 599-609, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36562941

RESUMO

BACKGROUND: Fundic gland polyps (FGP) of stomach are benign, while some hyperplastic polyps (HP) may harbor dysplasia or malignancy. Conventional white light endoscopy (WLE) cannot reliably distinguish FGP from HP. We investigated the role of image-enhanced endoscopy in differentiating FGP from HP. METHODS: Patients with gastric polyps were recruited prospectively. The characteristics of the polyps were assessed using WLE and magnification narrow band imaging (mNBI). The microsurface, intervening space (IS), and microvascular (V) features of polyps were evaluated on mNBI. The pattern characteristic of FGP and HP were determined. Histopathology of polyps was the gold standard for diagnosis. Finally, in the validation phase, five endoscopists applied the characteristic features identified in this study to predict the type of gastric polyp and their performance was assessed. RESULTS: Forty-five patients with a total of 70 gastric polyps (HP-46, FGP-24) were included in this study. On mNBI, the pattern characteristic of HP included peripheral curved type of white structures forming large circular/villous loops (microsurface), enlarged intervening space, and microvessels appearing as dark patches in the intervening space (p<0.001 vs. FGP). These were noted in 95.7% HP. In contrast, 95.8% FGP had a pattern characterized by dotted/elliptical/tubular white structures (microsurface), normal width of intervening space, and microvessels surrounding the white structures in a network pattern. This IS-V pattern classification had an accuracy of >90% in the validation phase with intra-class correlation coefficient of 0.95. The accuracy of mNBI was higher than WLE (97.1% vs. 67%) in predicting the type of gastric polyp. CONCLUSIONS: Image-enhanced endoscopy with mNBI (IS-V pattern) performs very well in differentiating HP from FGP.


Assuntos
Pólipos , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologia , Pólipos/diagnóstico , Endoscopia Gastrointestinal , Hiperplasia
13.
J Cancer Res Ther ; 18(6): 1646-1650, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36412425

RESUMO

Objective: The objective of our study was to evaluate the detection rate of prostate cancer by digital rectal examination (DRE) and serum prostate-specific antigen (PSA) levels followed by standard 12-core transrectal ultrasound (TRUS)-guided prostate biopsy. Materials and Methods: After screening of patients presenting with lower urinary tract symptoms (LUTS) using DRE and serum PSA level, we enrolled patients for TRUS-guided 12-core prostate biopsy. Indications included PSA level ≥4 ng/ml and/or suspicious DRE findings. A retrospective analysis was done to find out the correlation between suspicious rectal examination and various serum PSA levels in detection of cancer prostate. Results: A total of 847 patients were screened for cancer prostate during our study period (May 2012-February 2020). Among them, 823 patients who underwent prostate biopsy were analyzed. Prostate cancer was detected in 330 cases (40.09%). Mean age of patient (years) with and without prostate cancer was 66.25 ± 9.45 and 64.3 ± 8.96 years, respectively. Median value of serum PSA in patients positive for cancer was 33 ± 260 ng/ml compared to patients without cancer, who had a median value of 9 ± 64 ng/ml (P-value of <0.0001). The detection rate of cancer based on suspicious DRE findings irrespective of PSA was 52.18% (251/481), compared to 45.46% (311/684) using a PSA cut-off of ≥4.0 ng/ml alone. Among 330 patients with positive biopsy, 19 (5.75%) had a PSA level <4 ng/ml and they were identified based on suspicious DRE alone. Conclusion: Suspicious DRE was significantly associated with detection of prostate cancer across all PSA levels. Patients with PSA <4 can harbor prostate malignancy and such cases can be detected by use of DRE in screening of all patients with LUTS.


Assuntos
Neoplasias da Próstata , Urologia , Masculino , Humanos , Exame Retal Digital , Antígeno Prostático Específico , Estudos Retrospectivos , Atenção Terciária à Saúde , Neoplasias da Próstata/patologia
14.
Indian Pediatr ; 59(10): 782-801, 2022 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-36263494

RESUMO

JUSTIFICATION: Anemia in children is a significant public health problem in our country. Comprehensive National Nutrition Survey 2016-18 provides evidence that more than 50% of childhood anemia is due to an underlying nutritional deficiency. The National Family Health Survey-5 has reported an increase in the prevalence of anemia in the under-five age group from 59% to 67.1% over the last 5 years. Clearly, the existing public health programs to decrease the prevalence of anemia have not shown the desired results. Hence, there is a need to develop nationally acceptable guidelines for the diagnosis, treatment and prevention of nutritional anemia. OBJECTIVE: To review the available literature and collate evidence-based observations to formulate guidelines for diagnosis, treatment and prevention of nutritional anemia in children. PROCESS: These guidelines have been developed by the experts from the Pediatric Hematology-Oncology Chapter and the Pediatric and Adolescent Nutrition (PAN) Society of the Indian Academy of Pediatrics (IAP). Key areas were identified as: epidemiology, nomenclature and definitions, etiology and diagnosis of iron deficiency anemia (IDA), treatment of IDA, etiology and diagnosis of vitamin B12 and/or folic acid deficiency, treatment of vitamin B12 and/or folic acid deficiency anemia and prevention of nutritional anemia. Each of these key areas were reviewed by at least 2 to 3 experts. Four virtual meetings were held in November, 2021 and all the key issues were deliberated upon. Based on review and inputs received during meetings, draft recommendations were prepared. After this, a writing group was constituted which prepared the draft guidelines. The draft was circulated and approved by all the expert group members. RECOMMENDATIONS: We recommend use of World Health Organization (WHO) cut-off hemoglobin levels to define anemia in children and adolescents. Most cases suspected to have IDA can be started on treatment based on a compatible history, physical examination and hemogram report. Serum ferritin assay is recommended for the confirmation of the diagnosis of IDA. Most cases of IDA can be managed with oral iron therapy using 2-3 mg/kg elemental iron daily. The presence of macro-ovalocytes and hypersegmented neutrophils, along with an elevated mean corpuscular volume (MCV), should raise the suspicion of underlying vitamin B12 (cobalamin) or folic acid deficiency. Estimation of serum vitamin B12 and folate level are advisable in children with macrocytic anemia prior to starting treatment. When serum vitamin B12 and folate levels are unavailable, patients should be treated using both drugs. Vitamin B12 should preferably be started 10-14 days ahead of oral folic acid to avoid precipitating neurological symptoms. Children with macrocytic anemia in whom a quick response to treatment is required, such as those with pancytopenia, severe anemia, developmental delay and infantile tremor syndrome, should be managed using parenteral vitamin B12. Children with vitamin B12 deficiency having mild or moderate anemia may be managed using oral vitamin B12 preparations. After completing therapy for nutritional anemia, all infants and children should be advised to continue prophylactic iron-folic acid (IFA) supplementation as prescribed under Anemia Mukt Bharat guidelines. For prevention of anemia, in addition to age-appropriate IFA prophylaxis, routine screening of infants for anemia at 9 months during immunization visit is recommended.


Assuntos
Anemia Ferropriva , Anemia Macrocítica , Anemia , Deficiência de Ácido Fólico , Hematologia , Deficiência de Vitamina B 12 , Lactente , Adolescente , Humanos , Criança , Pré-Escolar , Deficiência de Ácido Fólico/complicações , Deficiência de Ácido Fólico/epidemiologia , Deficiência de Vitamina B 12/diagnóstico , Deficiência de Vitamina B 12/epidemiologia , Anemia/diagnóstico , Anemia/epidemiologia , Anemia/etiologia , Vitamina B 12 , Anemia Ferropriva/complicações , Ácido Fólico/uso terapêutico , Ferro/uso terapêutico , Anemia Macrocítica/complicações , Hemoglobinas/análise , Ferritinas
15.
Biomed Pharmacother ; 154: 113654, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36067568

RESUMO

The growth of cancerous cells and their responses towards substantial therapeutics are primarily controlled by inflammations (acute and chronic) and inflammation-associated products, which either endorse or repress tumor progression. Additionally, major signaling pathways, including NF-κB, STAT3, inflammation-causing factors (cytokines, TNF-α, chemokines), and growth-regulating factors (VEGF, TGF-ß), are vital regulators responsible for the instigation and resolution of inflammations. Moreover, the conventional chemotherapeutics have exhibited diverse limitations, including poor pharmacokinetics, unfavorable chemical properties, poor targetability to the disease-specific disease leading to toxicity; thus, their applications are restricted in inflammation-mediated cancer therapy. Furthermore, nanotechnology has demonstrated potential benefits over conventional chemotherapeutics, such as it protected the incorporated drug/bioactive moiety from enzymatic degradation within the systemic circulation, improving the physicochemical properties of poorly aqueous soluble chemotherapeutic agents, and enhancing their targetability in specified carcinogenic cells rather than accumulating in the healthy cells, leading reduced cytotoxicity. Among diverse nanomaterials, polyester-based nanoparticulate delivery systems have been extensively used to target various inflammation-mediated cancers. This review summarizes the therapeutic potentials of various polyester nanomaterials (PLGA, PCL, PLA, PHA, and others)-based delivery systems targeting multiple signaling pathways related to inflammation-mediated cancer.


Assuntos
Antineoplásicos , Neoplasias , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Sistemas de Liberação de Medicamentos , Humanos , Inflamação/tratamento farmacológico , Nanomedicina , Neoplasias/patologia , Poliésteres , Transdução de Sinais
16.
Chem Biol Interact ; 365: 110048, 2022 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-35932910

RESUMO

Mucus gel constitutes of heavily cross-linked mucin fibers forming a viscoelastic, dense porous network that coats all the exposed epithelia not covered with the skin. The layer provides protection to the underlying gastrointestinal, respiratory, and female reproductive tracts, in addition to the organs such as the surface of eye by trapping the pathogens, irritants, environmental fine particles, and potentially hazardous foreign matter. However, this property of mucus gel poses a substantial challenge for realizing the localized and sustained drug delivery across the mucosal surfaces. The mucus permeating particles that spare the protective properties of mucus gel improve the therapeutic potency of the drugs aimed at the management of diseases, including sexually transmitted infections, lung cancer, irritable bowel disease, degenerative eye diseases and infections, and cystic fibrosis. As such, the mucoadhesive materials conjugated with drug molecules display a prolonged retention time in the mucosal gel that imparts a sustained release of the deliberated drug molecules across the mucosa. The contemporarily developed mucus penetrating materials for drug delivery applications comprise of a finer size, appreciable hydrophilicity, and a neutral surface to escape the entrapment within the cross-inked mucus fibers. Pertaining to the mucus secretion as a first line of defence in respiratory tract in response to the invading physical, chemical, and biological pathogens, the development of mucus penetrating materials hold promise as a stalwart approach for revolutionizing the respiratory drug delivery paradigm. The present review provides an epigrammatic collation of the mucus penetrating/mucoadhesive materials for achieving a controlled/sustained release of the cargo pharmaceutics and drug molecules across the respiratory mucus barrier.


Assuntos
Nanopartículas , Transporte Biológico , Preparações de Ação Retardada/análise , Sistemas de Liberação de Medicamentos , Feminino , Humanos , Muco , Nanopartículas/química
17.
Antioxidants (Basel) ; 11(7)2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35883869

RESUMO

A nanosized food-grade quercetin-loaded nanoemulsion (QNE) system comprising capmul MCM NF (oil) and cremophor RH 40 (surfactant) was developed using a high-speed homogenization technique. The developed QNE was studied for its significant neuroprotective (anti-Parkinsonism) and cytotoxicity (anticancer) effects against Caenorhabditis elegans (C. elegans) strains and human cancer cells, respectively. HR-TEM studies revealed that the QNE was spherical with a mean globule size of ~50 nm. Selected area electron diffraction (SAED) studies results demonstrated that QNE was amorphous. In vivo results show that QNE potentially reduced the α-Syn aggregation, increased mitochondrial and fat content, and improved the lifespan in transgenic C. elegans strain NL5901. QNE significantly downregulated the reactive oxygen species (ROS) levels in wild-type C. elegans strain N2. In vitro results of the MTT assay show that QNE significantly exhibited chemotherapeutic effects in all treated human cancer cells in an order of cytotoxicity: HeLa cells > A549 cells > MIA PaCa-2 cells, based on the IC50 values at 24 h. Conclusively, the QNE showed improved solubility, targetability, and neuroprotective effects against the PD-induced C. elegans model, and also cytotoxicity against human cancer cells and could be potentially used as an anti-Parkinson's or anticancer agent.

18.
Indian J Pathol Microbiol ; 65(3): 689-691, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35900504

RESUMO

Adrenal myelolipoma is a benign tumor-like growth, composed of mature fat cells and bone marrow elements. We report a case of a 44-year lady who presented with a complaint of pain in the abdomen. The only positive finding was contrast-enhanced computed tomography (CECT) whole abdomen, which was suggestive of heterogeneously enhancing hypodense lesion of size 130 mm × 105 mm with few calcifications and 103 mm × 75 mm with intralesional fat attenuation in right and left adrenals. Rest laboratory parameters were normal. Only a few cases so far have been reported for bilateral adrenal myelolipoma but what stands out in our case is its giant size and bilaterality, managed surgically without any complications.


Assuntos
Neoplasias das Glândulas Suprarrenais , Lipoma , Mielolipoma , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/cirurgia , Glândulas Suprarrenais/patologia , Humanos , Mielolipoma/diagnóstico por imagem , Mielolipoma/cirurgia , Tomografia Computadorizada por Raios X
19.
J Biochem Mol Toxicol ; 36(10): e23174, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35861662

RESUMO

Respiratory diseases (RDs), such as chronic obstructive pulmonary disease, cystic fibrosis, asthma, and pneumonia, are associated with significant morbidity and mortality. Treatment usually consists of antibiotics and steroids. Relevant published literature reviews, studies, and clinical trials were accessed from institutional and electronic databases. The keywords used were respiratory diseases, steroids, antibiotics, and combination of steroids and antibiotics. Selected articles and literature were carefully reviewed. Antibiotics are often prescribed as the standard therapy to manage RDs. Types of causative respiratory pathogens, spectrum of antibiotics activity, route of administration, and course of therapy determine the type of antibiotics that are prescribed. Despite being associated with good clinical outcome, treatment failure and recurrence rate are still high. In addition, antibiotic resistance has been widely reported due to bacterial mutations in response to the use of antibiotics, which render them ineffective. Nevertheless, there has been a growing demand for corticosteroids (CS) and antibiotics to treat a wide variety of diseases, including various airway diseases, due to their immunosuppressive and anti-inflammatory properties. The use of CS is well established and there are different formulations based on the diseases, such as topical administration, tablets, intravenous injections, and inhaled preparations. Both antibiotics and CS possess similar properties in terms of their anti-inflammatory effects, especially regulating cytokine release. Thus, the current review examines and discusses the different applications of antibiotics, CS, and their combination in managing various RDs. Drawbacks of these interventions are also discussed.


Assuntos
Antibacterianos , Esteroides , Corticosteroides/uso terapêutico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Anti-Inflamatórios , Citocinas , Esteroides/uso terapêutico
20.
Nanomaterials (Basel) ; 12(13)2022 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-35808122

RESUMO

In the present study, nickel ferrite (NiFe2O4)-based smart magnetic nanoparticles were fabricated and coated with methionine. Physiochemical characterization of the obtained Met-NiFe2O4 nanoparticles revealed the presence of methionine coating over the nanoparticle surface. Drug release study indicated that Tet-Met-NiFe2O4 nanoparticles possess pH-responsive controlled drug release behavior for tetracycline (Tet). The drug loading content for Tet was found to be 0.27 mg/L of nanoparticles. In vitro cytotoxicity test showed that the Met-NiFe2O4 nanoparticles is biocompatible. Moreover, this magnetic nanostructured material shown strong anticancer property as these nanomaterials significantly reduced the viability of A375 cells when compared to free Tet solution. In addition, Tet-Met-NiFe2O4 nanoparticles also showed strong antibacterial activity against different bacterial pathogens.

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