Clinical Advances of siRNA-Based Nanotherapeutics for Cancer Treatment

Cancer is associated with single or multiple gene defects. Recently, much research has focused on incorporating genetic materials as one of the means to treat various types of carcinomas. RNA interference (RNAi) conveys an alternative genetic approach for cancer patients, especially when conventional medications fail. RNAi involves the inhibition of expression of specific messenger RNA that signals for uncontrollable cell growth and proliferation, most notably with carcinoma cells. This molecular technology is promising as genetic materials allow us to overcome issues associated with chemotherapeutic agents including organ damage associated with severe drug toxicities. Nonetheless, vast challenges impede successful gene therapy application, including low tumor localization, low stability and rapid clearance from the blood circulation. Owing to the limited treatment opportunities for the management of cancer, the development of effective siRNA carrier systems involving nanotherapeutics has been extensively explored. Over the past years, several siRNA nanotherapeutics have undergone a period of clinical investigation, with some demonstrating promising antitumor activities and safety profiles. Extensive observation of siRNA-nanoparticles is necessary to ensure commercial success. Therefore, this review mainly focuses on the progress of siRNAs-loaded nanoparticles that have undergone clinical trials for cancer treatment. The status of the siRNA nanotherapeutics is discussed, allowing comprehensive understanding of their gene-mediated therapeutics

Correlation between antibiotic consumption and the occurrence of multidrug-resistant organisms in a Malaysian tertiary hospital:a 3-year observational study

Inappropriate use of antibiotics has been shown to contribute to the occurrence of multidrug-resistant organisms (MROs). A surveillance study was performed in the largest tertiary care hospital in Kuala Lumpur, Malaysia, from 2018 to 2020 to observe the trends of broad-spectrum antibiotics (beta-lactam/beta-lactamases inhibitors (BL/BLI), extended-spectrum cephalosporins (ESC), and fluoroquinolones (FQ)) and antibiotics against MRO (carbapenems, polymyxins, and glycopeptides) usage and the correlation between antibiotic consumption and MROs. The correlation between 3-year trends of antibiotic consumption (defined daily dose (DDD)/100 admissions) with MRO infection cases (per 100 admissions) was determined using a Jonckheere-Terpstra test and a Pearson’s Correlation coefficient. The antimicrobial resistance trend demonstrated a positive correlation between ESC and FQ towards the development of methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum beta-lactamase (ESBL)-producing Klebsiella spp, ESBL-producing Escherichia coli (E. coli), and MRO Acinetobacter baumannii (A. baumannii). Increasing carbapenem consumption was positively correlated with the occurrence of ESBL-producing Klebsiella spp and E. coli. Polymyxin use was positively correlated with ESBL-producing Klebsiella spp, MRO A. baumannii, and carbapenem-resistant Enterobacteriaceae. The findings reinforced concerns regarding the association between MRO development, especially with a surge in ESC and FQ consumption. Stricter use of antimicrobials is thus crucial to minimise the risk of emerging resistant organisms

Strontium Sulfite: A New pH-Responsive Inorganic Nanocarrier to Deliver Therapeutic siRNAs to Cancer Cells

Inorganic nanoparticles hold great potential in the area of precision medicine, particularly for treating cancer owing to their unique physicochemical properties, biocompatibility and improved pharmacokinetics properties compared to their organic counterparts. Here we introduce strontium sulfite nanoparticles as new pH-responsive inorganic nanocarriers for efficient transport of siRNAs into breast cancer cells. We employed the simplest nanoprecipitation method to generate the strontium sulfite nanoparticles (SSNs) and demonstrated the dramatic roles of NaCl and d-glucose in particle growth stabilization in order to produce even smaller nanosize particles (Na-Glc-SSN) with high affinity towards negatively charged siRNA, enabling it to efficiently enter the cancer cells. Moreover, the nanoparticles were found to be degraded with a small drop in pH, suggesting their potential capability to undergo rapid dissolution at endosomal pH so as to release the payload. While these particles were found to be nontoxic to the cells, they showed higher potency in facilitating cancer cell death through intracellular delivery and release of oncogene-specific siRNAs targeting ros1 and egfr1 mRNA transcripts, than the strontium sulfite particles prepared in absence of NaCl and d-glucose, as confirmed by growth inhibition assay. The mouse plasma binding analysis by Q-TOF LC-MS/MS demonstrated less protein binding to smaller particles of Na-Glc-SSNs. The biodistribution studies of the particles after 4 h of treatment showed Na-Glc-SSNs had less off-target distribution than SSNs, and after 24 h, all siRNAs were cleared from all major organs except the tumors. ROS1 siRNA with its potential therapeutic role in treating 4T1-induced breast tumor was selected for subsequent in vivo tumor regression study, revealing that ROS1 siRNA-loaded SSNs exerted more significant anti-tumor effects than Na-Glc-SSNs carrying the same siRNA following intravenous administration, without any systemic toxicity. Thus, strontium sulfite emerged as a powerful siRNA delivery tool with potential applications in cancer gene therapy

Corak taburan ruang-masa semut (Hymenoptera: Formicidae) di ekosistem sawit, Endau Rompin, Pahang

Kajian ini dijalankan bagi mengetahui corak taburan ruang-masa semut (Hymenoptera: Formicidae) dan memahami ekologi ruang semut di ekosistem sawit di Endau Rompin, Pahang. Persampelan dijalankan selama empat bulan berturut-turut di tiga jenis tanah iaitu tanah liat (A1 & A2), tanah gambut dalam (B1 & B2) dan tanah gambut cetek (C1 & C2). Kaedah perangkap lubang digunakan bagi mensampel semut yang mencari makanan di atas tanah. Sejumlah 3,968 individu semut berjaya diperoleh, mewakili 13 genus dalam empat subfamili. Anoplolepis mencatatkan bilangan individu paling melimpah iaitu sebanyak 1,692 individu (45.75%) diikuti dengan Pheidole (862 individu; 23.31%) dan Paratrechina (228 individu; 6.17%). Dalam tanah liat, Anoplolepis ialah genus yang paling melimpah manakala bagi tanah gambut dalam dan cetek, Pheidole adalah genus yang paling melimpah berbanding genus yang lain. Ujian Khi kuasa-dua (dua hala) mengenal pasti perbezaan yang signifikan (p 1; p 0.05). Corak taburan ruang-masa setempat bagi subfamili semut adalah sangat dinamik dengan perubahan corak kelompok dan luang yang berbeza pada bulan yang berlainan. Gambaran awal corak taburan ruang-masa setempat bagi semut di ekosistem sawit yang diperoleh dalam kajian ini menunjukkan hubung kait ekologi dan lakuan beberapa genus walau pun secara kolektifnya dicerap pada peringkat subfamili. Kajian lanjut bagi melihat asosiasi ruang-masa antara subfamili dirasakan perlu bagi memperjelaskan lagi ekologi lakuan dan interaksi dalam kalangan komuniti berfungsi semut