KARAKTERISASI SENYAWA PENGKONTRAS CT-SCAN TERARAH AuNP-PAMAM G4-NIMOTUZUMAB MELALUI SIMULASI MENGGUNAKAN 198AuNP-PAMAM G4-NIMOTUZUMAB

KARAKTERISASI SENYAWA PENGKONTRAS CT-SCAN TERARAH AuNPPAMAM G4-NIMOTUZUMAB MELALUI SIMULASI MENGGUNAKAN 198AuNP-PAMAM G4-NIMOTUZUMAB. Modalitas Computed Tomography Scan (CT-Scan) dapat digunakan untuk diagnosa cedera tulang (bone injuries), visualisasi paru-paru, dada dan untuk mendeteksi kanker. Untuk meningkatkan kualitas hasil pencitraan dengan CT-Scan pada pasien yang akan dicitra, kadang-kadang diberi/dinjeksi terlebih dahulu dengan senyawa pengkontras berbasis iodium. Senyawa pengkontras berbasis iodium mempunyai beberapa keterbatasan yaitu diantaranya harus diimport dari luar negeri, toksisitas yang cukup tinggi dan tingkat pencitraannya masih pada ditingkat anatomi. Nanopartikel emas telah banyak dikembangkan dan digunakan sebagai pengganti senyawa pengkontras berbasis iodium. Dalam penelitian ini, telah dilakukan penyiapan senyawa pengkontras CT-Scan terarah/ pencitraan tingkat molekulerAu Nano Partikel-PoliAmido Amin Generasi 4-Nimotuzumab (AuNP-PAMAM G4-Nimotuzumab) yang didapatkan dengan mengkonyugasikan AuNP terbungkus PAMAM G4 dengan Nimotuzumab. Karakterisasi hasil konyugasi AuNP-PAMAMG4-Nimotuzumab, dilakukan dengan menggunakan Kromatografi Cair Kinerja Tinggi (KCKT), Sodium Dodecyl Sulphate Polyacrilamide Gel Electrophoresis (SDS page) dan Transmission Electron Microscope (TEM). Karakterisasi AuNP-PAMAMG4-Nimotuzumab Kromatografi Cair Kinerja Tinggi KCKT memberikan waktu retensi (rt) 5,2 menit yang sama dengan menit AuNP-PAMAM G4-Nimotuzumab yang ditandai radioaktif 198AuNP-PAMAM G4-Nimotuzumab berturut-turut 5,2 menit (detektor UV) dan 5,3 menit (detektor radioaktif)

Potent antiviral activity against HSV-1 and SARS-CoV-2 by antimicrobial peptoids

Viral infections, such as those caused by Herpes Simplex Virus-1 (HSV-1) and SARS-CoV-2, affect millions of people each year. However, there are few antiviral drugs that can effectively treat these infections. The standard approach in the development of antiviral drugs involves the identification of a unique viral target, followed by the design of an agent that addresses that target. Antimicrobial peptides (AMPs) represent a novel source of potential antiviral drugs. AMPs have been shown to inactivate numerous different enveloped viruses through the disruption of their viral envelopes. However, the clinical development of AMPs as antimicrobial therapeutics has been hampered by a number of factors, especially their enzymatically labile structure as peptides. We have examined the antiviral potential of peptoid mimics of AMPs (sequence-specific N-substituted glycine oligomers). These peptoids have the distinct advantage of being insensitive to proteases, and also exhibit increased bioavailability and stability. Our results demonstrate that several peptoids exhibit potent in vitro antiviral activity against both HSV-1 and SARS-CoV-2 when incubated prior to infection. In other words, they have a direct effect on the viral structure, which appears to render the viral particles non-infective. Visualization by cryo-EM shows viral envelope disruption similar to what has been observed with AMP activity against other viruses. Furthermore, we observed no cytotoxicity against primary cultures of oral epithelial cells. These results suggest a common or biomimetic mechanism, possibly due to the differences between the phospholipid head group makeup of viral envelopes and host cell membranes, thus underscoring the potential of this class of molecules as safe and effective broad-spectrum antiviral agents. We discuss how and why differing molecular features between 10 peptoid candidates may affect both antiviral activity and selectivity

Peptide-mimetic treatment of Pseudomonas aeruginosa in a mouse model of respiratory infection

The rise of drug resistance has become a global crisis, with >1 million deaths due to resistant bacterial infections each year. Pseudomonas aeruginosa, in particular, remains a serious problem with limited solutions due to complex resistance mechanisms that now lead to more than 32,000 multidrug-resistant (MDR) infections and over 2000 deaths in the U.S. annually. While the emergence of resistant bacteria has become ominously common, identification of useful new drug classes has been limited over the past over 40 years. We found that a potential novel therapeutic, the peptide-mimetic TM5, is effective at killing P. aeruginosa and displays sufficiently low toxicity in mammalian cells to allow for use in treatment of infections. Interestingly, TM5 kills P. aeruginosa more rapidly than traditional antibiotics, within 30–60 min in vitro, and is effective against a range of clinical isolates, including extensively drug resistant strains. In vivo, TM5 significantly reduced bacterial load in the lungs within 24 h compared to untreated mice and demonstrated few adverse effects. Taken together, these observations suggest that TM5 shows promise as an alternative therapy for MDR P. aeruginosa respiratory infections

Peptide-mimetic treatment of Pseudomonas aeruginosa in a mouse model of respiratory infection

The rise of drug resistance has become a global crisis, with >1 million deaths due to resistant bacterial infections each year. Pseudomonas aeruginosa, in particular, remains a serious problem with limited solutions due to complex resistance mechanisms that now lead to more than 32,000 multidrugresistant (MDR) infections and over 2000 deaths in the U.S. annually. While the emergence of resistant bacteria has become ominously common, identification of useful new drug classes has been limited over the past over 40 years. We found that a potential novel therapeutic, the peptide-mimetic TM5, is effective at killing P. aeruginosa and displays sufficiently low toxicity in mammalian cells to allow for use in treatment of infections. Interestingly, TM5 kills P. aeruginosa more rapidly than traditional antibiotics, within 30–60 min in vitro, and is effective against a range of clinical isolates, including extensively drug resistant strains. In vivo, TM5 significantly reduced bacterial load in the lungs within 24 h compared to untreated mice and demonstrated few adverse effects. Taken together, these observations suggest that TM5 shows promise as an alternative therapy for MDR P. aeruginosa respiratory infections

Deceleration of Fusion–Fission Cycles Improves Mitochondrial Quality Control during Aging

Mitochondrial dynamics and mitophagy play a key role in ensuring mitochondrial quality control. Impairment thereof was proposed to be causative to neurodegenerative diseases, diabetes, and cancer. Accumulation of mitochondrial dysfunction was further linked to aging. Here we applied a probabilistic modeling approach integrating our current knowledge on mitochondrial biology allowing us to simulate mitochondrial function and quality control during aging in silico. We demonstrate that cycles of fusion and fission and mitophagy indeed are essential for ensuring a high average quality of mitochondria, even under conditions in which random molecular damage is present. Prompted by earlier observations that mitochondrial fission itself can cause a partial drop in mitochondrial membrane potential, we tested the consequences of mitochondrial dynamics being harmful on its own. Next to directly impairing mitochondrial function, pre-existing molecular damage may be propagated and enhanced across the mitochondrial population by content mixing. In this situation, such an infection-like phenomenon impairs mitochondrial quality control progressively. However, when imposing an age-dependent deceleration of cycles of fusion and fission, we observe a delay in the loss of average quality of mitochondria. This provides a rational why fusion and fission rates are reduced during aging and why loss of a mitochondrial fission factor can extend life span in fungi. We propose the ‘mitochondrial infectious damage adaptation’ (MIDA) model according to which a deceleration of fusion–fission cycles reflects a systemic adaptation increasing life span

A Genome-Wide Immunodetection Screen in S. cerevisiae Uncovers Novel Genes Involved in Lysosomal Vacuole Function and Morphology

Vacuoles of yeast Saccharomyces cerevisiae are functionally analogous to mammalian lysosomes. Both are cellular organelles responsible for macromolecular degradation, ion/pH homeostasis, and stress survival. We hypothesized that undefined gene functions remain at post-endosomal stage of vacuolar events and performed a genome-wide screen directed at such functions at the late endosome and vacuole interface – ENV genes. The immunodetection screen was designed to identify mutants that internally accumulate precursor form of the vacuolar hydrolase carboxypeptidase Y (CPY). Here, we report the uncovering and initial characterizations of twelve ENV genes. The small size of the collection and the lack of genes previously identified with vacuolar events are suggestive of the intended exclusive functional interface of the screen. Most notably, the collection includes four novel genes ENV7, ENV9, ENV10, and ENV11, and three genes previously linked to mitochondrial processes – MAM3, PCP1, PPE1. In all env mutants, vesicular trafficking stages were undisturbed in live cells as assessed by invertase and active α-factor secretion, as well as by localization of the endocytic fluorescent marker FM4-64 to the vacuole. Several mutants exhibit defects in stress survival functions associated with vacuoles. Confocal fluorescence microscopy revealed the collection to be significantly enriched in vacuolar morphologies suggestive of fusion and fission defects. These include the unique phenotype of lumenal vesicles within vacuoles in the novel env9Δ mutant and severely fragmented vacuoles upon deletion of GET4, a gene recently implicated in tail anchored membrane protein insertion. Thus, our results establish new gene functions in vacuolar function and morphology, and suggest a link between vacuolar and mitochondrial events

Mitochondrial function as a determinant of life span

Average human life expectancy has progressively increased over many decades largely due to improvements in nutrition, vaccination, antimicrobial agents, and effective treatment/prevention of cardiovascular disease, cancer, etc. Maximal life span, in contrast, has changed very little. Caloric restriction (CR) increases maximal life span in many species, in concert with improvements in mitochondrial function. These effects have yet to be demonstrated in humans, and the duration and level of CR required to extend life span in animals is not realistic in humans. Physical activity (voluntary exercise) continues to hold much promise for increasing healthy life expectancy in humans, but remains to show any impact to increase maximal life span. However, longevity in Caenorhabditis elegans is related to activity levels, possibly through maintenance of mitochondrial function throughout the life span. In humans, we reported a progressive decline in muscle mitochondrial DNA abundance and protein synthesis with age. Other investigators also noted age-related declines in muscle mitochondrial function, which are related to peak oxygen uptake. Long-term aerobic exercise largely prevented age-related declines in mitochondrial DNA abundance and function in humans and may increase spontaneous activity levels in mice. Notwithstanding, the impact of aerobic exercise and activity levels on maximal life span is uncertain. It is proposed that age-related declines in mitochondrial content and function not only affect physical function, but also play a major role in regulation of life span. Regular aerobic exercise and prevention of adiposity by healthy diet may increase healthy life expectancy and prolong life span through beneficial effects at the level of the mitochondrion

Keterlibatan Akademisi dalam Menanggulangi Dampak Covid-19 terhadap Masyarakat melalui Aksi Berbagi Sembako

Aspek ekonomi menerima dampak ±60% dari bencana pandemi. Dampak ini umumnya merupakan bagain dari proses tindakan pencegahan dan pengendalian terhadap penyebaran Virus. Indonesia merupakan satu negara yang sedang dilanda bencana pandemi Covid-19. Berbagai kebijakan dalam upaya pencegahan telah dilakukan oleh pemerintah, yang berdampak pada aspek ekonomi masyarakat. Masyarakat pedesaan merupakan masyarakat yang rentan mengalami resiko kerugian akibat pandemi Covid-19. Oleh karena itu, pengabdian ini bertujuan untuk meringankan dampak pandemi Covid-19 terhadap masyarakat di beberapa desa yang menerima dampak dari kebijakan pencegahan penyebaran Covid-19. Pengabdian ini menjadi satu wujud nyata keterlibatan akademisi dalam mengurangi dampak Covid-19 terhadap masyarakat di pedesaan. Pengabdian ini menggunakan model kolaborasi sebagai metode dalam pelaksanaannya. Hasil dari kegiatan ini terdapat 400 keluarga yang mendapat dampak ekonomi dari pandemi Covid-19 yang tersebar di tiga desa. Pengabdian kepada masyarakat dengan model kolaborasi dinilai sebagai tindakan yang baik dalam mewujudkan keterlibatan perguruan tinggi dengan tetap melakukan social distancing