Aging-associated changes in microRNA expression profile of internal anal sphincter smooth muscle: Role of microRNA-133a.

A comprehensive genomic and proteomic, computational, and physiological approach was employed to examine the (previously unexplored) role of microRNAs (miRNAs) as regulators of internal anal sphincter (IAS) smooth muscle contractile phenotype and basal tone. miRNA profiling, genome-wide expression, validation, and network analyses were employed to assess changes in mRNA and miRNA expression in IAS smooth muscles from young vs. aging rats. Multiple miRNAs, including rno-miR-1, rno-miR-340-5p, rno-miR-185, rno-miR-199a-3p, rno-miR-200c, rno-miR-200b, rno-miR-31, rno-miR-133a, and rno-miR-206, were found to be upregulated in aging IAS. qPCR confirmed the upregulated expression of these miRNAs and downregulation of multiple, predicted targets (Eln, Col3a1, Col1a1, Zeb2, Myocd, Srf, Smad1, Smad2, Rhoa/Rock2, Fn1, Tagln v2, Klf4, and Acta2) involved in regulation of smooth muscle contractility. Subsequent studies demonstrated an aging-associated increase in the expression of miR-133a, corresponding decreases in RhoA, ROCK2, MYOCD, SRF, and SM22α protein expression, RhoA-signaling, and a decrease in basal and agonist [U-46619 (thromboxane A2 analog)]-induced increase in the IAS tone. Moreover, in vitro transfection of miR-133a caused a dose-dependent increase of IAS tone in strips, which was reversed by anti-miR-133a. Last, in vivo perianal injection of anti-miR-133a reversed the loss of IAS tone associated with age. This work establishes the important regulatory effect of miRNA-133a on basal and agonist-stimulated IAS tone. Moreover, reversal of age-associated loss of tone via anti-miR delivery strongly implicates miR dysregulation as a causal factor in the aging-associated decrease in IAS tone and suggests that miR-133a is a feasible therapeutic target in aging-associated rectoanal incontinence

HMGCS2 is a key ketogenic enzyme potentially involved in type 1 diabetes with high cardiovascular risk.

Diabetes increases the risk of Cardio-vascular disease (CVD). CVD is more prevalent in type 2 diabetes (T2D) than type 1 diabetes (T1D), but the mortality risk is higher in T1D than in T2D. The pathophysiology of CVD in T1D is poorly defined. To learn more about biological pathways that are potentially involved in T1D with cardiac dysfunction, we sought to identify differentially expressed genes in the T1D heart. Our study used T1D mice with severe hyperglycemia along with significant deficits in echocardiographic measurements. Microarray analysis of heart tissue RNA revealed that the T1D mice differentially expressed 10 genes compared to control. Using Ingenuity Pathway Analysis (IPA), we showed that these genes were significantly involved in ketogenesis, cardiovascular disease, apoptosis and other toxicology functions. Of these 10 genes, the 3-Hydroxy-3-Methylglutaryl-CoA Synthase 2 (HMGCS2) was the highest upregulated gene in T1D heart. IPA analysis showed that HMGCS2 was center to many biological networks and pathways. Our data also suggested that apart from heart, the expression of HMGCS2 was also different in kidney and spleen between control and STZ treated mice. In conclusion, The HMGCS2 molecule may potentially be involved in T1D induced cardiac dysfunction

Role of differentially expressed microRNA-139-5p in the regulation of phenotypic internal anal sphincter smooth muscle tone.

The present study focused on the role of microRNA-139-5p (miRNA-139-5p) in the regulation of basal tone in internal anal sphincter (IAS). Applying genome-wide miRNA microarrays on the phenotypically distinct smooth muscle cells (SMCs) within the rat anorectrum, we identified miRNA-139-5p as differentially expressed RNA repressor with highest expression in the purely phasic smooth muscle of anococcygeus (ASM) vs. the truly tonic smooth muscle of IAS. This pattern of miRNA-139-5p expression, previously shown to target ROCK2, was validated by target prediction using ingenuity pathway (IPA) and by qPCR analyses. Immunoblotting, immunocytochemistry (ICC), and functional assays using IAS tissues and cells subjected to overexpression/knockdown of miRNA-139-5p confirmed the inverse relationship between miRNA-139-5p and ROCK2 expressions/IAS tone. Overexpression of miRNA-139-5p caused a decrease, while knockdown by anti-miRNA-139-5p caused an increase in the IAS tone; these tissue contractile responses were confirmed by single-cell contraction using magnetic twisting cytometry (MTC). These findings suggest miRNA-139-5p is capable of significantly influencing the phenotypic tonicity in smooth muscle via ROCK2: a lack of tone in ASM may be associated with the suppression of ROCK2 by high expression of miRNA-139-5p, whereas basal IAS tone may be associated with the persistence of ROCK2 due to low expression of miRNA-139-5p

The Acceptance of COVID-19 Vaccine: The Projection from the First Year of COVID-19 Pandemic in Indonesia

The Pandemic of COVID-19 affected not only the health sector but also other sectors. Herd immunity through vaccination was recommended by experts. This study purposed to describe the acceptance of the COVID-19 vaccine and to discover predictive factors of COVID-19 vaccine acceptance in Indonesia. This is a cross-sectional study. Data collection used an online platform conducted in August 2020. The questionnaire based on Survey Tool and Guidance by WHO Regional Office for Europe. Logistic regression was run to identify associated factors and to build a predictive model of vaccine acceptance. There were 164 respondents aged 19 – 56 years. About 70.1 percent of respondents showed a willingness to accept the vaccine for COVID-19. The predictive model consisted of age, perceived probability that has been infected and trust in government press releases with performance reaching 73 percent.  The trust of people in the government was the most important key to engaging people in vaccination. Evidence-based messaging delivered regularly by the government and consistent action between the government and health officers would educate and lead people's risk perceived and the decision to be vaccinated

NFκB activation and stimulation of chemokine production in normal human macrophages by the gadolinium-based magnetic resonance contrast agent Omniscan: possible role in the pathogenesis of nephrogenic systemic fibrosis.

OBJECTIVE: Nephrogenic systemic fibrosis (NSF) is a generalised fibrotic disorder occurring in certain individuals with renal insufficiency exposed to gadolinium-based contrast agents (GdBCA) for MRI. Histopathological examination of affected tissues shows increased numbers of activated macrophages. To elucidate the mechanisms responsible for macrophage activation, the effects of the GdBCA Omniscan on normal human macrophage global gene expression, chemokine production and nuclear factor κB (NFκB) activation was examined. METHODS: Normal human monocyte-derived macrophages were incubated with Omniscan (50 mM) and their gene expression analysed by microarrays and real-time PCR. Macrophage chemokine production was assayed by multiplex ELISA. NFκB activation was assessed by NFκB nuclear localisation and quantitation of intracellular levels of inducible nitric oxide synthase (iNOS) protein. A specific cell-permeable NFκB peptide inhibitor was used to abrogate NFκB stimulation of chemokine and iNOS protein levels. CCL8/MCP-2 in affected skin of patients with NSF was examined by indirect immunofluorescence. RESULTS: Omniscan caused a profound change in the transcriptome of differentiated human normal macrophages in vitro, including a large increase in the expression of genes encoding CC and CXC chemokines. It induced rapid nuclear localisation of NFκB and stimulation of iNOS protein levels and chemokine production which were blocked by an NFκB inhibitory peptide. CCL8/MCP-2, the most upregulated chemokine following in vitro macrophage exposure to Omniscan, was strongly increased in NSF-affected skin. CONCLUSION: The GdBCA Omniscan induces potent stimulation of macrophage gene expression, NFκB activation and increased NFκB-mediated production of CC and CXC chemokines and iNOS. These alterations may play a crucial role in the pathogenesis of NSF

Effect of Protein Kinase C delta (PKC-δ) Inhibition on the Transcriptome of Normal and Systemic Sclerosis Human Dermal Fibroblasts In Vitro

Previous studies demonstrated that protein kinase C- δ (PKC-δ) inhibition with the selective inhibitor, rottlerin, resulted in potent downregulation of type I collagen expression and production in normal human dermal fibroblasts and abrogated the exaggerated type I collagen production and expression in fibroblasts cultured from affected skin from patients with the fibrosing disorder systemic sclerosis (SSc). To elucidate the mechanisms involved in the ability of PKC-δ to regulate collagen production in fibroblasts, we examined the effects of PKC-δ inhibition on the transcriptome of normal and SSc human dermal fibroblasts. Normal and SSc human dermal fibroblasts were incubated with rottlerin (5 µM), and their gene expression was analyzed by microarrays. Pathway analysis and gene ontology analysis of differentially expressed genes in each comparison were performed. Identification of significantly overrepresented transcriptional regulatory elements (TREs) was performed using the Promoter Analysis and Interaction Network Toolset (PAINT) program. PKC-δ activity was also inhibited using RNA interference (siRNA) and by treating fibroblasts with a specific PKC-δ inhibitory cell permeable peptide. Differential gene expression of 20 genes was confirmed using real time PCR. PKC-δ inhibition caused a profound change in the transcriptome of normal and SSc human dermal fibroblasts in vitro. Pathway and gene ontology analysis identified multiple cellular and organismal pathways affected by PKC-δ inhibition. Furthermore, both pathway and PAINT analyses indicated that the transcription factor NFκB played an important role in the transcriptome changes induced by PKC-δ inhibition. Multiple genes involved in the degradation of the extracellular matrix components were significantly reduced in SSc fibroblasts and their expression was increased by PKC-δ inhibition. These results indicate that isoform-specific inhibition of PKC-δ profibrotic effects may represent a novel therapeutic approach for SSc and other fibrotic diseases

Gerakan edukasi cegah stunting dari rumah pada masyarakat Kabupaten Maros

Stunting adalah kondisi gagal tumbuh pada anak yang memberikan banyak implikasi negatif jika tidak dicegah lebih dini. Salah satu faktor penghambat upaya penanganan stunting di masyarakat adalah rendahnya rendahnya pengetahuan mayarakat terkait gizi. Tujuan kegiatan ini adalan untuk memberikan edukasi bahwa stunting itu dapat dicegah dari rumah. Kegiatan pengabdian ini dilakukan dengan menggunakan metode CBR (Community-Based Research) dimana komunitas target berperan aktif dalam  proses kegiatan, dalam rangka meningkatkan efektifitas proses kerja dan menghasilkan sebuah rekomendasi yang benar-benar bermanfaat bagi perbaikan dan peningkatan kualitas kehidupan sosial mereka. Hasilnya metode edukasi yang dilakukan pada kegiatan ini (penyuluhan dan pembagian poster) efektif memperbaiki literasi komunitas target terkait informasi stunting. Oleh karena itu, diharapkan agar kegiatan serupa dapat terus dilakukan oleh tenaga kesehatan setempat termasuk untuk masalah kesehatan selain stunting

Immune clearance of attenuated rabies virus results in neuronal survival with altered gene expression.

Rabies virus (RABV) is a highly neurotropic pathogen that typically leads to mortality of infected animals and humans. The precise etiology of rabies neuropathogenesis is unknown, though it is hypothesized to be due either to neuronal death or dysfunction. Analysis of human brains post-mortem reveals surprisingly little tissue damage and neuropathology considering the dramatic clinical symptomology, supporting the neuronal dysfunction model. However, whether or not neurons survive infection and clearance and, provided they do, whether they are functionally restored to their pre-infection phenotype has not been determined in vivo for RABV, or any neurotropic virus. This is due, in part, to the absence of a permanent mark on once-infected cells that allow their identification long after viral clearance. Our approach to study the survival and integrity of RABV-infected neurons was to infect Cre reporter mice with recombinant RABV expressing Cre-recombinase (RABV-Cre) to switch neurons constitutively expressing tdTomato (red) to expression of a Cre-inducible EGFP (green), permanently marking neurons that had been infected in vivo. We used fluorescence microscopy and quantitative real-time PCR to measure the survival of neurons after viral clearance; we found that the vast majority of RABV-infected neurons survive both infection and immunological clearance. We were able to isolate these previously infected neurons by flow cytometry and assay their gene expression profiles compared to uninfected cells. We observed transcriptional changes in these cured neurons, predictive of decreased neurite growth and dysregulated microtubule dynamics. This suggests that viral clearance, though allowing for survival of neurons, may not restore them to their pre-infection functionality. Our data provide a proof-of-principle foundation to re-evaluate the etiology of human central nervous system diseases of unknown etiology: viruses may trigger permanent neuronal damage that can persist or progress in the absence of sustained viral antigen

Keracunan Pestisida Pada Petani Bawang Merah di Desa Pasui Kecamatan Buntu Batu Kabupaten Enrekang

Peningkatan hasil pertanian dan perkebunan dalam rangka memenuhi permintaan pasar, maka petani melakukan program berupa budi daya tanaman dengan cara pengolahan tanah, pemilihan bibit unggul, pemupukan yang tepat, perbaikan bercocok tanam serta sistem pengendalian atau pemberantasan hama terpacu dengan menggunakan pestisida. Petani sebagai pengguna pestisida mempunyai risiko tinggi terpapar pestisida yang mengakibatkan cacat tubuh dan kematian dan hasil peneliti menunjukkan tingginya angka kejadian keracunan di sebabkan oleh pestisida antara 20–50%. Tujuan penelitian ini untuk mengetahui factor yang berhuungan dengan kejadian keracunan pestisida pada petani bawang merah di Desa Pasui Kecamatan Buntu Batu Kabupaten Enrekang. Jenis penelitian ini merupakan penelitian survey analitik dengan pendekatan cross sectional study. Sampel sebanyak 157 orang dengan tehnik pengambilan secara Exhautice Sampling. Penelitian dilakukan di Desa Pasui Kecamatan Buntu Batu Kabupaten Enrekang. Dari hasil pengumpulan dan pengolahan data menunjukkan bahwa ada hubungan pengetahuan (p=0,000), sikap (p=0,000), penggunaan APD (p=0,000) dan Higiene Perorangan (p=0,000) dengan gejala keracunan pada petani bawang di Desa Pasui Kecamatan Buntu Batu Kabupaten Enrekang. Diharapkan kepada petani bawang di Desa Pasui Kecamatan Buntu Batu agar lebih meningkatkan pengetahuan, menjaga dan meningkatkan derajat kesehatannya, mengingat karena petani bawang tidak terlepas dari penggunaan pestisida sehingga ancaman keracunan akan semakin besar, maka sebaiknya mulai dini gunakan pestisida secara benar dan aman sehingga terhindar dari keracunan akibat pestisida   Kata Kunci: Pestisida, KeracunanPeningkatan hasil pertanian dan perkebunan dalam rangka memenuhi permintaan pasar, maka petani melakukan program berupa budi daya tanaman dengan cara pengolahan tanah, pemilihan bibit unggul, pemupukan yang tepat, perbaikan bercocok tanam serta sistem pengendalian atau pemberantasan hama terpacu dengan menggunakan pestisida. Petani sebagai pengguna pestisida mempunyai risiko tinggi terpapar pestisida yang mengakibatkan cacat tubuh dan kematian dan hasil peneliti menunjukkan tingginya angka kejadian keracunan di sebabkan oleh pestisida antara 20–50%. Tujuan penelitian ini untuk mengetahui factor yang berhuungan dengan kejadian keracunan pestisida pada petani bawang merah di Desa Pasui Kecamatan Buntu Batu Kabupaten Enrekang. Jenis penelitian ini merupakan penelitian survey analitik dengan pendekatan cross sectional study. Sampel sebanyak 157 orang dengan tehnik pengambilan secara Exhautice Sampling. Penelitian dilakukan di Desa Pasui Kecamatan Buntu Batu Kabupaten Enrekang. Dari hasil pengumpulan dan pengolahan data menunjukkan bahwa ada hubungan pengetahuan (p=0,000), sikap (p=0,000), penggunaan APD (p=0,000) dan Higiene Perorangan (p=0,000) dengan gejala keracunan pada petani bawang di Desa Pasui Kecamatan Buntu Batu Kabupaten Enrekang. Diharapkan kepada petani bawang di Desa Pasui Kecamatan Buntu Batu agar lebih meningkatkan pengetahuan, menjaga dan meningkatkan derajat kesehatannya, mengingat karena petani bawang tidak terlepas dari penggunaan pestisida sehingga ancaman keracunan akan semakin besar, maka sebaiknya mulai dini gunakan pestisida secara benar dan aman sehingga terhindar dari keracunan akibat pestisida   Kata Kunci: Pestisida, Keracuna

Hubungan Penggunaan Media Sosial dengan Perilaku Makan Mahasiswa di Kota Makassar

Internet, sebagai bagian dari perkembangan teknologi informasi banyak sekali memberikan kemudahan untuk penggunanya dan telah masuk dalam semua bagian sendi kehidupan. Penggunaan internet dan media sosial saat ini bukan hanya untuk kebutuhan edukasi semata, namun juga dipergunakan untuk hiburan, belanja, media sosial dan hal lainnya. Hasil Survei Pangan tahun 2018 menemukan bahwa penduduk yang berusia di atas 10 tahun di Indonesia mempunyai perilaku konsumsi makanan berlemak, berkolesterol, dan makanan gorengan 40,7%, konsumsi maknan asin 26,2%, dan konsumsi makanan manis 53,1%, dan perilaku kurang konsumsi sayur dan buah mencapai 93,6%. Berbanding lurus dengan penggunaan internet yang juga semakin meningkat. Maka dari itu peneliti tertarik untuk melihat bagaiman hubungan penggunaan media sosial dengan perilaku makan, khususnya mahasiswa yang notabene merupakan kelompok yang menggunakan gadget sangat aktif. Penelitian ini merupakan penelitian kuantitatif dengan pendekatan cross sectional, dengan sampel sebanyak 86 reseponden, yang diambil secara purposive sampling. Kesimpulan yang didapatkan dari hasil penelitian yaitu tidak ada hubungan durasi penggunaan media sosial dengan perilaku makan, hal tersebut ditunjukkan dengan p-value= 0,624 > 0,05. Tidak ada hubungan frekuensi penggunaan media sosial dengan perilaku makan, hal tersebut ditunjukkan dengan p-value= 0,440> 0,05. Ada hubungan akses media sosial terkait informasi makanan dengan perilaku makan. Hasil p-value= 0,125> 0,05 dengan nilai ORcrude (95% CI)= 2,805 (1,123-7,005).   Kata kunci: internet, perilaku makan, social mediaInternet, sebagai bagian dari perkembangan teknologi informasi banyak sekali memberikan kemudahan untuk penggunanya dan telah masuk dalam semua bagian sendi kehidupan. Penggunaan internet dan media sosial saat ini bukan hanya untuk kebutuhan edukasi semata, namun juga dipergunakan untuk hiburan, belanja, media sosial dan hal lainnya. Hasil Survei Pangan tahun 2018 menemukan bahwa penduduk yang berusia di atas 10 tahun di Indonesia mempunyai perilaku konsumsi makanan berlemak, berkolesterol, dan makanan gorengan 40,7%, konsumsi maknan asin 26,2%, dan konsumsi makanan manis 53,1%, dan perilaku kurang konsumsi sayur dan buah mencapai 93,6%. Berbanding lurus dengan penggunaan internet yang juga semakin meningkat. Maka dari itu peneliti tertarik untuk melihat bagaiman hubungan penggunaan media sosial dengan perilaku makan, khususnya mahasiswa yang notabene merupakan kelompok yang menggunakan gadget sangat aktif. Penelitian ini merupakan penelitian kuantitatif dengan pendekatan cross sectional, dengan sampel sebanyak 86 reseponden, yang diambil secara purposive sampling. Kesimpulan yang didapatkan dari hasil penelitian yaitu tidak ada hubungan durasi penggunaan media sosial dengan perilaku makan, hal tersebut ditunjukkan dengan p-value= 0,624 > 0,05. Tidak ada hubungan frekuensi penggunaan media sosial dengan perilaku makan, hal tersebut ditunjukkan dengan p-value= 0,440> 0,05. Ada hubungan akses media sosial terkait informasi makanan dengan perilaku makan. Hasil p-value= 0,125> 0,05 dengan nilai ORcrude (95% CI)= 2,805 (1,123-7,005).   Kata kunci: internet, perilaku makan, social medi