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OBJECTIVE: Angiogenesis is the process of forming new blood vessels from pre-existing vessels and occurs during development, wound healing, and tumor growth. In this review, we aimed to present a comprehensive view of various factors contributing to angiogenesis during carcinogenesis. Anti-angiogenesis agents prevent or slow down cancer growth by interrupting the nutrients and blood supply to the tumor cells, and thus can prove beneficial for treatment. METHOD: The discovery of several novel angiogenic inhibitors has helped to reduce both morbidity and mortality from several life-threatening diseases, such as carcinomas. There is an urgent need for a new comprehensive treatment strategy combining novel anti-angiogenic agents for the control of cancer. The article contains details of various angiogenic inhibitors that have been adopted by scientists to formulate and optimize such systems in order to make them suitable for cancer. RESULTS: The results of several researches have been summarized in the article and all of the data support the claim that anti-angiogenic agent is beneficial for cancer treatment. CONCLUSION: This review focuses on novel antiangiogenic agents that play a crucial role in controlling carcinogenesis.
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Background: Mycobacterium tuberculosis infection is transmitted among humans via airborne droplets. The drugs used in the initial treatment regimen for tuberculosis (TB) cross the placenta, raising some concerns regarding their safety during pregnancy may provide a more valid approach for evaluating the relative influence of various risk factors. Adverse events of anti-tuberculous (anti-TB) drug during pregnancy remain uncertain and controversial issues. Methods: We performed a systematic analysis to study the adverse events connected with anti-TB drugs usage during pregnancy. The risk of bias in the included studies was assessed using the Cochrane Collaboration criteria. Interstudy heterogeneity was assessed via Cochran's test. Assuming heterogeneity, a random-effects model was applied. Outcomes were pooled using the inverse variance method. Besides, a funnel plot was created to assess publication bias. We used Egger's linear regression test of funnel plot asymmetry, modified to accommodate inter-study heterogeneity. Effect estimates and confidence intervals for all studies were depicted on a forest plot. Results: The prevalence of total adverse events for all anti-TB drugs was 25.9 %. According to the drug category, the prevalence of total adverse events was 50 % for ethambutol, 32.6 % for the six-month directly observed treatment short-course (DOTS), 31.4 % for the nine-month DOTS, and 13.7 % for isoniazid. Conclusions: There is a high rate of reported adverse events associated with anti-TB drugs usage during pregnancy. We concluded that more high-quality clinical studies and research works are needed to reach a conclusive decision on the safety of the treatment of TB among pregnant women.
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Flavonoids are hydroxylated phenolic substances in vegetables, fruits, flowers, seeds, wine, tea, nuts, propolis, and honey. They belong to a versatile category of natural polyphenolic compounds. Their biological function depends on various factors such as their chemical structure, degree of hydroxylation, degree of polymerization conjugation, and substitutions. Flavonoids have gained considerable attention among researchers, as they show a wide range of pharmacological activities, including coronary heart disease prevention, antioxidative, hepatoprotective, anti-inflammatory, free-radical scavenging, anticancer, and anti-atherosclerotic activities. Plants synthesize flavonoid compounds in response to pathogen attacks, and these compounds exhibit potent antimicrobial (antibacterial, antifungal, and antiviral) activity against a wide range of pathogenic microorganisms. However, certain antibacterial flavonoids have the ability to selectively target the cell wall of bacteria and inhibit virulence factors, including biofilm formation. Moreover, some flavonoids are known to reverse antibiotic resistance and enhance the efficacy of existing antibiotic drugs. However, due to their poor solubility in water, flavonoids have limited oral bioavailability. They are quickly metabolized in the gastrointestinal region, which limits their ability to prevent and treat various disorders. The integration of flavonoids into nanomedicine constitutes a viable strategy for achieving efficient cutaneous delivery owing to their favorable encapsulation capacity and diminished toxicity. The utilization of nanoparticles or nanoformulations facilitates drug delivery by targeting the drug to the specific site of action and exhibits excellent physicochemical stability.
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Alzheimer's disease (AD) is a deadly, progressive, and irreversible brain condition that impairs cognitive abilities. Globally, it affects 32.6 million individuals, and if no viable therapies are available by 2050, that figure might rise to 139 million. The current course of treatment enhances cognitive abilities and temporarily relieves symptoms, but it does not halt or slow the disease's development. Additionally, treatments are primarily offered in conventional oral dosage forms, and conventional oral treatments lack brain specialization and cause adverse effects, resulting in poor patient compliance. A potential nanotechnology-based strategy can improve the bioavailability and specificity of the drug targeting in the brain. Furthermore, this review extensively summarizes the applications of nanomedicines for the effective delivery of drugs used in the management of AD. In addition, the clinical progress of nanomedicines in AD is also discussed, and the challenges facing the clinical development of nanomedicines are addressed in this article.
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Trastuzumab (TZB) is a new medicine, used to treat cancers of the breast and stomach. However, the cardiotoxic potential of this drug edges out its clinical advantages. The present study was designed to find out the effect of zingerone against trastuzumab-mediated cardiotoxicity in rats. In this study, five groups of rats with eight animals in each group were used. Group 1 was treated with normal saline, as a normal control (NC); Group 2 was treated with TZB (6 mg/kg/week-for five weeks) intraperitoneally as a toxic control. Groups 3 and 4 were pre-treated with zingerone (50 and 100 mg/kg, as per their body weight orally) along with five doses of TZB for five weeks, and Group 5 was treated with zingerone (100 mg/kg, body weight orally) as a control. TZB treatment showed cardiotoxicity as evidenced by increased levels of aspartate aminotransferase (AST), creatine kinase-myocardial band (CK-MB), lactate dehydrogenase (LDH), and lipid peroxidation (LPO) and decreased level of glutathione (GSH), and antioxidant enzymes such as glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-s- transferase (GST), catalase (CAT), and superoxide dismutase (SOD) activities. Zingerone pre-treatment significantly decreased the levels of AST, CK-MB, LDH, and LPO and increased GSH and antioxidant enzymes content toward their normal level. In the TZB-alone administered group, inflammatory cytokines (IL-2 and TNF-α) levels were also elevated. Pre-treatment with zingerone restored the level of IL-2 and TNF-α toward normal level. The current findings undoubtedly demonstrated zingerone's cardioprotective nature against TZB-mediated cardiotoxicity in rats with the evidence of histopathological recall.
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ß−sitosterol is the most abundant type of phytosterol or plant sterol and can be found in various plant dietary sources including natural oils, soy products, and nuts. Numerous studies have demonstrated the potential therapeutic and clinical applications of ß−sitosterol including lowering low-density lipoprotein and cholesterol levels, scavenging free radicals in the body, and interestingly, treating and preventing cancer. This study focuses on synthesizing and characterizing ß−sitosterol encapsulated Alginate/Chitosan nanoparticles (ß−sito−Alg/Ch/NPs) and evaluating their effectiveness in breast cancer treatment and their pharmacokinetic profile in vivo. The synthesized NPs, which incurred a mean size of 25 ± 1 nm, were extensively characterized in vitro for various parameters including surface charge and morphology. The NPs were further analyzed using DSC, FT-IR, thermogravimetry and X-ray diffraction studies. The release of ß−sito from NPs was carried out in a bio-relevant medium of pH 7.4 and pH 5.5 and samples were drawn off and analyzed under time frames of 0, 8, 16, 32, 64, 48, 80, and 96 h, and the best kinetic release model was developed after fitting drug release data into different kinetic models. The metabolic activity of MCF-7 cells treated with the prepared formulation was assessed. The radical scavenging potential of ß−sito−Alg/Ch/NPs was also studied. The pharmacokinetic parameters including Cmax, Tmax, half-life (t1/2), and bioavailability were measured for ß−sito−Alg/Ch/NPs as compared to ß−sito−suspension. The ß−sito−Alg/Ch/NPs stability was assessed at biological pH 7.4. The % drug release in PBS of pH 7.4 reportedly has shown 41 ± 6% vs. 11 ± 1% from ß−sito−Alg/Ch/NPs and ß−sito−suspension. In acidic pH 5.5 mimicking the tumor microenvironment has shown 75 ± 9% vs. 12 ± 4% drug release from ß−sito−Alg/Ch/NPs and ß−sito−suspension. When compared to the ß−sito−suspension, the ß−sito−Alg/Ch/NPs demonstrated greater cytotoxicity (p < 0.05) and ~3.41-fold higher oral bioavailability. Interestingly, this work demonstrated that ß−sito−Alg/Ch/NPs showed higher cytotoxicity due to improved bioavailability and antioxidant potential compared to the ß−sito−suspension.
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A validated ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed for the first-ever simultaneous analysis of neratinib, curcumin and internal standard (imatinib) using acetonitrile as the liquid-liquid extraction medium. On a BEH C18 (100 mm × 2.1 mm, 1.7 µm) column, the analytes were separated isocratically using acetonitrile (0.1% formic acid):0.002M ammonium acetate. The flow rate was set at 0.5 mL.min-1. The authors utilized multiple reaction monitoring-based transitions for the precursor-to-product ion with m/z 557.099 â 111.928 for neratinib, m/z 369.231 â 176.969 curcumin and m/z 494.526 â 394.141 for imatinib during the study. Validation of the method as per United States Food and Drug Administration requirements for linearity (5-40 ng mL-1), accuracy and precision, stability, matrix effect, etc. were investigated and were observed to be acceptable. Afterward, we evaluated the method for establishing its greenness profile by using two greenness assessment tools and found it green. Overall, a reliable green UPLC-MS/MS method was devised and used to estimate neratinib and curcumin in human plasma simultaneously.
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In the present study, erythromycin (EM)-loaded nanostructured lipid carriers (NLCs) were prepared by the emulsification and ultra-sonication method. EM-NLCs were optimized by central composite design using the lipid (A), pluronic F127 (B) and sonication time (C) as independent variables. Their effects were evaluated on particle size (Y1) and entrapment efficiency (Y2). The optimized formulation (EM-NLCs-opt) showed a particle size of 169.6 ± 4.8 nm and entrapment efficiency of 81.7 ± 1.4%. EM-NLCs-opt further transformed into an in-situ gel system by using the carbopol 940 and chitosan blend as a gelling agent. The optimized EM-NLCs in situ gel (EM-NLCs-opt-IG4) showed quick gelation and were found to be stable for more than 24 h. EM-NLCs-opt-IG4 showed prolonged drug release compared to EM in situ gel. It also revealed significant high permeation (56.72%) and flux (1.51-fold) than EM in situ gel. The irritation and hydration study results depicted no damage to the goat cornea. HET-CAM results also confirmed its non-irritant potential (zero score). EM-NLCs-opt-IG4 was found to be isotonic and also showed significantly (p < 0.05) higher antimicrobial activity than EM in situ gel. The findings of the study concluded that NLCs laden in situ gel is an alternative delivery of erythromycin for the treatment of bacterial conjunctivitis.