Engineering Of Gold Nanoparticles For Drug Delivery

Due to their ease of synthesis, versatile surface chemistry, ease of imaging, and biocompatibility, gold nanoparticles (AuNPs) are employed as drug delivery devices in the treatment of respiratory problems associated with spinal cord injury (SCI). We have developed a method for the synthesis of a tripartite nanoconjugate comprised of an AuNP drug carrier chemically conjugated to a transporter protein (wheat germ agglutinin coupled to horseradish peroxidase or WGA-HRP) and to potent SCI drugs. The therapeutic efficacy and biodistribution were studied in a validated animal model. Our results show that a single administration of the nanoconjugate improved diaphragmatic activity at a much lower dosage than the effective systemic drug dosage and restored the respiratory drive. The effects lasted for 4 weeks. A biodistribution study using inductively coupled plasma mass spectrometry on the same animal model shows that the nanoconjugate was successful in targeting the respiratory neurons in the medulla by detecting the presence of gold in the medulla and spinal cord. The AuNPs are also applied in triple negative breast cancer treatment. By conjugating the surface modified AuNPs with a non-soluble drug, the solubility has been increased and introduced cancer cell death after administration. The nanoconjugate structure was determined by UV-vis spectroscopy, transmission electron microscopy, dynamic light scattering, thermogravimetric analysis, and mass spectrometry

SEKOLAH SEPAKBOLA USIA MUDA DI BANDA ACEH

Sepakbola merupakan olahraga yang sangat populer dan digemari di dunia, begitu juga di Indonesia. Tak heran jika hampir semua negara di dunia berlomba-lomba menggalang prestasi membanggakan di cabang olahraga ini. Indonesia belum mampu meraih prestasi yang membanggakan di cabang olahraga sepakbola, bahkan Indonesia sulit bersaing di kancah Internasional. Klub-klub sepakbola Aceh juga tidak dapat berbuat banyak di kompetisi internal, sedangkan Aceh merupakan salah satu provinsi yang banyak memunculkan pemain muda berbakat.Kualitas persepakbolaan di Indonesia yang rendah dan minim prestasi ini dikarenakan kurang pembinaan dan pelatihan pemain mulai dari usia dini untuk didik menjadi pemain profesional. Sarana pelatihan yang ada di Indonesia belum serius ke arah profesional seperti akademi sepakbola di Eropa. Di negara-negara maju dalam sepakbola, prestasi tim nasional pada umumnya dilatarbelakangi oleh sistem dan proses pembinaan klub yang sudah mapan.Sekolah sepakbola usia muda di Banda Aceh merupakan sebuah sarana pelatihan dan pembinaan sepakbola pemain usia dini di Banda Aceh. Pemain tersebut akan dididik, dilatih dan dibina sejak dini sebagai usaha pembibitan pemain sepakbola Aceh yang potensial. Sekolah sepakbola ini berlokasi di Lhong Raya, sesuai dengan rencana pengembangan kawasan pusat olahraga di Banda Aceh. Dengan mengusung tema arsitektur metafora, diharapkan bangunan sekolah sepakbola ini dapat menjadi objek arsitektur yang melekat di masyarakat.Tahap awal dalam proses perancangan Sekolah Sepakbola Usia Muda di Banda Aceh ini adalah studi literatur data dan studi banding. Selanjutnya permasalahan yang ada diidentifikasi dan dianalisis sesuai dengan batasan perancangan. Dalam lingkup batasan tema arsitektur metafora dan kondisi iklim setempat selanjutnya melahirkan konsep perancangan sesuai dengan hasil analisis.Kata kunci: olahraga, sekolah, sepakbolaBanda Ace

Therapeutic enhancement of radiation and immunomodulation by gold nanoparticles in triple negative breast cancer

Gold nanoparticles (AuNPs) have been shown to enhance cancer radiotherapy (RT) gain by localizing the absorption of radiation energy in the tumor while sparing surrounding normal tissue from radiation toxicity. Previously, we showed that AuNPs enhanced RT induced DNA damage and cytotoxicity in MCF7 breast cancer cells. Interestingly, we found that cancer cells exhibited a size-dependent AuNPs intracellular localization (4 nm preferentially in the cytoplasm and 14 nm in the nucleus). We extended those studies to an in vivo model and examined the AuNPs effects on RT cytotoxicity, survival and immunomodulation of tumor microenvironment (TME) in human triple negative breast cancer (TNBC) xenograft mouse model. We also explored the significance of nanoparticle size in these AuNPs\u27 effects. Mice treated with RT and RT plus 4 nm or 14 nm AuNPs showed a significant tumor growth delay, compared to untreated animals, while dual RT plus AuNPs treatment exhibited additive effect compared to either RT or AuNPs treatment alone. Survival log-rank test showed significant RT enhancement with 14 nm AuNP alone; however, 4 nm AuNPs did not exhibit RT enhancement. Both sizes of AuNPs enhanced RT induced immunogenic cell death (ICD) that was coupled with significant macrophage infiltration in mice pretreated with 14 nm AuNPs. These results showing significant AuNP size-dependent RT enhancement, as evident by both tumor growth delay and overall survival, reveal additional underlying immunological mechanisms and provide a platform for studying RT multimodal approaches for TNBC that may be combined with immunotherapies, enhancing their effect

Case Report: Ensartinib for gastric epithelioid inflammatory myofibrosarcoma with STRN-ALK fusion

Epithelioid inflammatory myofibroblastic sarcoma (EIMS) is a highly aggressive malignant subtype of inflammatory myofibroblastoma (IMT) associated with poor prognosis. IMT can occur in various parts of the body, most frequently in the lungs, followed by the mesentery, omentum, retroperitoneum, and pelvis, among other areas; however, it is exceptionally rare in the stomach. Anaplastic lymphoma kinase (ALK) is a critical driver of lung cancer development and is currently the “gold standard” target for non-small cell lung cancer treatment. However, there are few reports on the use of ALK inhibitors for EIMS, necessitating further investigation. A male patient with postoperative inflammatory myofibroblastic sarcoma of the stomach received postoperative chemotherapy and had a stable outcome. However, a repeat CT scan performed 11 months later revealed disease progression. The patient later underwent immunohistochemistry testing that indicated ALK positivity, and next-generation sequencing revealed STRN-ALK fusion. Ensartinib 225 mg qd was administered as recommended, and the patient experienced only mild pruritus and no adverse effects such as rash. Eight months after CT follow-up, the patient’s subseptal soft tissue nodules had decreased, and the outcome was assessed as a partial response. The findings of this case report introduce a novel strategy for treating ALK-positive EIMS that utilizes ensartinib, a drug with previously demonstrated success in the treatment of ALK-positive cancer

A study of risk factors for tuberculous meningitis among patients with tuberculosis in China: An analysis of data between 2012 and 2019

PurposeThe present study aimed to explore the risk factors for tuberculous meningitis (TBM) among patients with tuberculosis (TB).MethodsThis retrospective study was conducted on patients with TB who were hospitalized in Beijing Chest Hospital between January 2012 and December 2019. Demographic and clinical data of patients with TB were extracted from electronic medical records using a standardized data collection system. Logistic regression was used to analyze the risk factors associated with TBM.ResultsOf the total number of 22,988 cases enrolled, 3.1% were cases of TBM, which included 127 definite and 581 probable TBM, respectively. Multivariate analysis showed that definite TBM was significantly associated with patients aged < 30 years [adjusted odds ratio (aOR) = 3.015, 95% confidence interval (CI): (1.451–6.266)], who were farmers [aOR = 1.490, 95%CI: (1.020–2.177)], with miliary pulmonary TB [aOR = 105.842, 95%CI: (71.704–156.235)], and with malnutrition [aOR = 2.466, 95%CI: (1.110–5.479)]. Additionally, probable TBM was significantly associated with patients aged < 30 years [aOR = 2.174, 95% CI: (1.450–3.261)], aged 30–59 years [aOR = 1.670, 95% CI: (1.222–2.282)], who were farmers [aOR = 1.482, 95%CI: (1.203–1.825)], with miliary pulmonary TB [aOR = 108.696, 95%CI: (87.122–135.613)], and with a digestive system TB [aOR = 2.906, 95%CI: (1.762–4.793)].ConclusionAn age of < 30 years, being a farmer, and having miliary pulmonary TB were risk factors for TBM among patients with TB. Further screening of patients with TB with aforementioned characteristics could facilitate clinicians to identify patients with TBM at an early stage

Prolylcarboxypeptidase Alleviates Hypertensive Cardiac Remodeling by Regulating Myocardial Tissue Angiotensin II

Background Prolonged activation of angiotensin II is the main mediator that contributes to the development of heart diseases, so converting angiotensin II into angiotensin 1-7 has emerged as a new strategy to attenuate detrimental effects of angiotensin II. Prolylcarboxypeptidase is a lysosomal pro-X carboxypeptidase that is able to cleave angiotensin II at a preferential acidic pH optimum. However, insufficient attention has been given to the cardioprotective functions of prolylcarboxylpeptidase. Methods and Results We established a CRISPR/CRISPR-associated protein 9-mediated global prolylcarboxylpeptidase-knockout and adeno-associated virus serotype 9-mediated cardiac prolylcarboxylpeptidase overexpression mouse models, which were challenged with the angiotensin II infusion (2 mg/kg per day) for 4 weeks, aiming to investigate the cardioprotective effect of prolylcarboxylpeptidase against hypertensive cardiac hypertrophy. Prolylcarboxylpeptidase expression was upregulated after 2 weeks of angiotensin II infusion and then became downregulated afterward in wild-type mouse myocardium, suggesting its compensatory function against angiotensin II stress. Moreover, angiotensin II-treated prolylcarboxylpeptidase-knockout mice showed aggravated cardiac remodeling and dampened cardiac contractility independent of hypertension. We also found that prolylcarboxylpeptidase localizes in cardiomyocyte lysosomes, and loss of prolylcarboxylpeptidase led to excessive angiotensin II levels in myocardial tissue. Further screening demonstrated that hypertrophic prolylcarboxylpeptidase-knockout hearts showed upregulated extracellular signal-regulated kinases 1/2 and downregulated protein kinase B activities. Importantly, adeno-associated virus serotype 9-mediated restoration of prolylcarboxylpeptidase expression in prolylcarboxylpeptidase-knockout hearts alleviated angiotensin II-induced hypertrophy, fibrosis, and cell death. Interestingly, the combination of adeno-associated virus serotype 9-mediated prolylcarboxylpeptidase overexpression and an antihypertensive drug, losartan, likely conferred more effective protection than a single treatment protocol to mitigate angiotensin II-induced cardiac dysfunction. Conclusions Our data demonstrate that prolylcarboxylpeptidase protects the heart from angiotensin II-induced hypertrophic remodeling by controlling myocardial angiotensin II levels

Innovative inbuilt moving bed biofilm reactor for nitrogen removal applied in household aquarium

An innovative inbuilt moving bed biofilm reactor (MBBR) was created to protect fish from nitrogen in a household aquarium. During the 90 experimental days, the ammonia nitrogen (NH4+-N) concentration in the aquarium with the inbuilt MBBR was always below 0.5 mg/L, which would not threaten the fish. Concurrently, nitrite and nitrate nitrogen concentrations were always below 0.05 mg/L and 4.5 mg/L, respectively. However, the blank contrast aquarium accumulated 1.985 mg/L NH4+-N on the 16th day, which caused the fish to die. The suspended biofilms could achieve the specific NH4+-N removal rate of 45.43 g/m3/d. Biofilms presented sparsely with filamentous structures and showed certain degrees of roughness. The bacterial communities of the suspended biofilms and the sediment were statistically different (p < 0.05), reflected in denitrifying and nitrifying bacteria. In particular, the relative abundance of Nitrospira reached 1.4%, while the genus was barely found in sediments. The suspended biofilms showed potentials for nitrification function with the predicted sequence numbers of ammonia monooxygenase [1.14.99.39] and hydroxylamine dehydrogenase [EC:1.7.2.6] of 220 and 221, while the values of the sediment were only 5 and 1. This study created an efficient NH4+-N removal inbuilt MBBR for household aquariums and explored its mechanism to afford a basis for its utilization

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Publisher Copyright: © 2022, The Author(s).Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.Peer reviewe

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Abstract Background Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk