The concept of establishing autonomous occupational safety and health in hospitals: an abstraction proposal

Currently, in many hospitals in Indonesia, the Occupation Safety and Health Committee in the Hospital (OSH-CH) is evenly distributed. It is based on the instruction of the Health Department of the Republic of Indonesia that obliges each hospital to establish the committee the main function of which is to prepare necessary equipment for risk management essential in the hospital. OSH-CH must also be responsible for upgrading the accreditation process of the hospital as to work units on occupational safety, fire control and disaster preparedness. However, in fact, OSH-CH has insignificant power as many people, especially the manager of the hospital, may expect. OSH-CH tends to be stagnant and irresponsive. In other words, it tends to be non-professional. The reasons are: (1) the staff of OSH-CH work as part-timers, (2) they have minimum understanding about OSH, (3) they do not have incentive and enough budget, (4) it is only to show that the hospital "obeys" the orders of the authorities, (5) managerial support within the hospital is minimal, and (6) there are no significant cases of work-related accidents and illnesses. These explain the reasons why OSH-CH has no significant power and the progress of its program is so slow. For some large hospitals this often leads to inefficiency and ineffectiveness of the organization, and in some cases it may even tend to create difficulties in conducting risk control. Based on these reasons, it is recommended to establish an autonomous OSH work unit that operates on the basis of structural and formal organizational operations. The paper aims to discuss the proposed concept of the autonomous OSH work unit established in hospitals, particularly for large hospitals. It is urgent to develop long-term capacities of the unit to sustain its reliability.     

Epitope mapping of gp350/220 conserved domain of epstein barr virus to develop nasopharyngeal carcinoma (npc) vaccine

Nasopharyngeal carcinoma (NPC) is a malignant tumor in the nasopharyngeal epithelial cells that caused by many factors, one of which is the viral infection of EBV (Epstein Barr Virus). The standard treatments to cure NPC still have not been encouraging. The prevention through vaccination is an effective way to stop the disease. However, EBV vaccine being able to cover all variants of virus is still not available yet. Therefore, we identified the conserved region of glycoprotein 350/220 of EBV which has immunogenic and antigenic properties. The glycoprotein 350/220 is viral surface protein responsible to bind CR2 receptor, mediated EBV to enter the host cell. The conserved domain is crucial for EBV in infecting host cells. Further, by blocking CR2 binding domain of gp350/220 using antibody will inhibit EBV's spreading, and provoke an immune system to eliminate the virus in a patient. Glycoprotein 350/220 from all variants of Epstein-Barr virus was retrieved from NCBI. The conserved domain of gp350/220 was identified by aligning the protein sequences and structures. The polymorphic structure was used as a template for docking analysis to identify the resemblance of amino acid from polymorphic variants of gp350/220 that binds CR2. The epitope mapping of gp350/220 was done by Discotope BepiPred method. The result revealed that the conserved region of gp350/220 was predicted to have an epitope, QNPVYLIPETVPYIKWDNC residue, and it does not have any similarities to the human's cell surface protein. Therefore, it can be used as a reference to develop vaccine to prevent NPC.     

Identifications small molecules inhibitor of p53-mortalin complex for cancer drug using virtual screening

Mortalin was over expressed in tumor cells and bind to p53 protein. This interaction was suggested to promote sequestration of p53 in the cytoplasm, thereby inhibiting its nuclear activity. The p53 is a tumor suppressor that is essential for the prevention of cancer development and loss of p53 function is one of the early events in immortalization of human cells. Therefore, abrogation p53-mortalin interaction using small molecule is guaranteed stop cancer cell grow. However study interaction of p53-mortalin, and its inhibition using small molecule is still challenging because specific site of mortalin that bind to p53, vice versa, is still debatable. This study has aims to analyze the p53-binding site of mortalin using molecular docking and to screen drug-like compounds that have potential as inhibitors of p53-mortalin interaction using virtual screening. The result showed that the lowest energy binding of p53-mortalin complex is -31.89 kcal/mol, and p53 protein bind to substrate binding domain of mortalin (THR433; VAL435; LEU436; LEU437; PRO442; ILE558; LYS555). Furthermore, the p53-binding domain of mortalin was used as receptor to screen 9000 drug-like compounds from ZINC database using molecular docking program Auto Dock Vina in PyRx 0.8 (Virtual Screening Tools). Here, we have identified three drug-like compounds that are ZINC01019934, ZINC00624418 and ZINC00664532 adequate to interrupt stability of p53-mortalin complex that warrant for anticancer agent.     

Fire risks in forest carbon projects in Indonesia

It is well known that forest carbon or sink projects have not been included in theClean Development Mechanism (CDM), one of the flexible mechanisms created under the Kyoto Protocol. The main concern for postponing sink projects is related to issues of methodology and integrity. Project eligibility needs to be judged in a transparent manner if they are real, measurable,provide long-term benefits to mitigate climate change, and provide additional benefits to those thatwould occur in the absence of a certified project. One of the biggest challenges in implementing sink projects is fire risks and the associated biophysical and socio-economic underlying causes. This study attempts to assess fire probability and use it as a tool to estimate fire risk in carbon sink projects. Fire risks may not only threatenongoing projects but may also cause leakage of carbon stocks in other areas, especially in pro-tected areas. This exercise was carried out in the Berbak National Park located in Jambi Province, Sumatra, Indonesia and the surrounding areas. Fire probability is associated with (i) the means by which access to a given area is possible, and (ii) vegetation type or fuel load. Although most fires were intentionally ignited, fire escape iscommon and is enhanced by long spell of dry weather. When this occurs, secondary road was themost frequently used means, and it was certainly the case during 1997/1998 big fires when dam-age to natural vegetation (natural and secondary forests) was substantial. Burnt natural vegetationwas 120000 ha or 95% of the total burnt areas, and released more than 7 Mt of carbon into the atmosphere.     

Selective killing of cancer cells by Ashwagandha leaf extract and its component Withanone involves ROS signaling

Background and Purpose

Ashwagandha is a popular Ayurvedic herb used in Indian traditional home medicine. It has been assigned a variety of health-promoting effects of which the mechanisms remain unknown. We previously reported the selective killing of cancer cells by leaf extract of Ashwagandha (i-Extract) and its purified component Withanone. In the present study, we investigated its mechanism by loss-of-function screening (abrogation of i-Extract induced cancer cell killing) of the cellular targets and gene pathways.

Methodology/Principal Findings

Randomized ribozyme library was introduced into cancer cells prior to the treatment with i-Extract. Ribozymes were recovered from cells that survived the i-Extract treatment. Gene targets of the selected ribozymes (as predicted by database search) were analyzed by bioinformatics and pathway analyses. The targets were validated for their role in i-Extract induced selective killing of cancer cells by biochemical and molecular assays. Fifteen gene-targets were identified and were investigated for their role in specific cancer cell killing activity of i-Extract and its two major components (Withaferin A and Withanone) by undertaking the shRNA-mediated gene silencing approach. Bioinformatics on the selected gene-targets revealed the involvement of p53, apoptosis and insulin/IGF signaling pathways linked to the ROS signaling. We examined the involvement of ROS-signaling components (ROS levels, DNA damage, mitochondrial structure and membrane potential) and demonstrate that the selective killing of cancer cells is mediated by induction of oxidative stress.

Conclusion

Ashwagandha leaf extract and Withanone cause selective killing of cancer cells by induction of ROS-signaling and hence are potential reagents that could be recruited for ROS-mediated cancer chemotherapy.     

Stress chaperone mortalin regulates human melanogenesis

In order to identify the cellular factors involved in human melanogenesis, we carried out shRNA-mediated loss-of-function screening in conjunction with induction of melanogenesis by 1-oleoyl-2-acetyl-glycerol (OAG) in human melanoma cells using biochemical and visual assays. Gene targets of the shRNAs (that caused loss of OAG-induced melanogenesis) and their pathways, as determined by bioinformatics, revealed involvement of proteins that regulate cell stress response, mitochondrial functions, proliferation, and apoptosis. We demonstrate, for the first time, that the mitochondrial stress chaperone mortalin is crucial for melanogenesis. Upregulation of mortalin was closely associated with melanogenesis in in vitro cell-based assays and clinical samples of keloids with hyperpigmentation. Furthermore, its knockdown resulted in compromised melanogenesis. The data proposed mortalin as an important protein that may be targeted to manipulate pigmentation for cosmetic and related disease therapeutics.     

Rhizomucor miehei lipase immobilized on reinforced chitosan–chitin nanowhiskers support for synthesis of eugenyl benzoate

An alternative environmentally benign support was prepared from chitosan–chitin nanowhiskers (CS/CNWs) for covalent immobilization of Rhizomucor miehei lipase (RML) to increase the operational stability and recyclability of RML in synthesizing eugenyl benzoate. The CS/CNWs support and RML-CS/CNWs were characterized using X-ray diffraction, fluorescent microscopy, and Fourier transform infrared spectroscopy. Efficiency of the RML-CS/CNWs was compared to the free RML to synthesize eugenyl benzoate for parameters: reaction temperature, stirring rate, reusability, and thermal stability. Under optimal experimental conditions (50°C, 250?rpm, catalyst loading 3?mg/mL), a twofold increase in yield of eugenyl benzoate was observed for RML-CS/CNWs as compared to free RML, with the former achieving maximum yield of the ester at 62.1% after 5?hr. Results demonstrated that the strategy adopted to prepare RML-CS/CNWs was useful, producing an improved and prospectively greener biocatalyst that supported a sustainable process to prepare eugenyl benzoate. Moreover, RML-CS/CNWs are biodegradable and perform esterification reactions under ambient conditions as compared to the less eco-friendly conventional acid catalyst. This research provides a facile and promising approach for improving activity of RML in which the resultant RML-CS/CNWs demonstrated good operational stability for up to eight successive esterification cycles to synthesize eugenyl benzoate.