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( Faysal Bin Hamid ),( Jinsun Kim ),( Cha-gyun Shin ) 한국미생물 · 생명공학회 2017 Journal of microbiology and biotechnology Vol.27 No.2
The foamy viruses are currently considered essential for development as vectors for gene delivery. Previous studies demonstrated that prototype foamy virus (PFV) can infect and replicate prevalently in a variety of cell types for its exclusive replication strategy. However, the virus-host interaction, especially PFV-transportin3 (TNPO3), is still poorly understood. In our investigation of the role of TNPO3 in PFV infection, we found lower virus production in TNPO3 knockdown (KD) cells compared with wild-type 293T cells. PCR analysis revealed that viral DNAs were mostly altered to circular forms: both 1-long terminal repeat (1-LTR) and 2-LTR in TNPO3 KD cells. We therefore suggest that TNPO3 is required for successful PFV replication, at least at/after the nuclear entry step of viral DNA. These findings highlight the obscure mysteries of PFV-host interaction and the requirement of TNPO3 for productive infection of PFV in 293T cells.
Cellular and viral determinants of retroviral nuclear entry
Hamid, Faysal Bin,Kim, Jinsun,Shin, Cha-Gyun Canadian Science Publishing 2016 Canadian journal of microbiology Vol.62 No.1
<P>Retroviruses must integrate their cDNA into the host genome to generate proviruses. Viral DNA-protein complexes interact with cellular proteins and produce pre-integration complexes, which carry the viral genome and cross the nuclear pore channel to enter the nucleus and integrate viral DNA into host chromosomal DNA. If the reverse transcripts fail to integrate, linear or circular DNA species such as 1- and 2-long terminal repeats are generated. Such complexes encounter numerous cellular proteins in the cytoplasm, which restrict viral infection and protect the nucleus. To overcome host cell defenses, the pathogens have evolved several evasion strategies. Viral proteins often contain nuclear localization signals, allowing entry into the nucleus. Among more than 1000 proteins identified as required for HIV infection by RNA interference screening, karyopherins, cleavage and polyadenylation specific factor 6, and nucleoporins have been predominantly studied. This review discusses current opinions about the synergistic relationship between the viral and cellular factors involved in nuclear import, with focus on the unveiled mysteries of the host-pathogen interaction, and highlights novel approaches to pinpoint therapeutic targets.</P>
Apoptotic events induced by prototype foamy virus infection
김진선,Faysal Bin Hamid,신차균 한국통합생물학회 2016 Animal cells and systems Vol.20 No.1
Foamy virus infection induces cytopathology in several cell types from different species. But the exact mechanism is still unknown. In this study, we have investigated the mechanism of cell death induced by prototype foamy virus (PFV) infection in baby hamster kidney (BHK 21) cell lines. PFV induces apoptosis by exhibiting morphological alterations such as chromatin condensation, blebbing, and nuclear fragmentation. In addition, PFV infection causes chromosomal DNA fragmentation, up-regulation of Bax, and activation of caspase-3, but not caspase-8. Up-regulation of Bax initiates the translocation of cytochrome-c from mitochondria to the cytoplasm, suggesting predominantly to the mitochondrial-mediated pathway. Blocking apoptosis using caspase inhibitors increased PFV-infected BHK 21 cell viability. Although blocking apoptosis resulted in reduced progeny release, maximal accumulation of PFV was found in apoptosis-blocked cells. This report provides the first experimental evidence of apoptosis induced by PFV infection, which will provide valuable insights for foamy viral pathology.
Recurrence Risk and Prognostic Parameters in Stage I Rectal Cancers
Cihan, Sener,Kucukoner, Mehmet,Ozdemir, Nuriye,Dane, Faysal,Sendur, Mehmet Ali Nahit,Yazilitas, Dogan,Urakci, Zuhat,Durnali, Ayse,Yuksel, Sinemis,Aksoy, Sercan,Colak, Dilsen,Seker, Mehmet Metin,Taskoy Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.13
Background: The standard therapy for stage I rectum cancer is surgical resection. Currently, there is no strong evidence to suggest that any type of adjuvant therapy is beneficial. The risks of local relapse and distant metastasis are higher in rectal tumors. Therefore, while there is no clearly defined absolute indication for adjuvant therapy in lymph node negative colon cancers, rectum tumors that are T3N0 and higher require adjuvant treatment. Due to the more aggressive nature of rectal cancers, we explored the clinical and pathologic factors that could predict the risk of relapse in Stage I (T1-T2) disease and whether there was any progression-free survival benefit to adjuvant therapy. Materials and Methods: This multicenter study was carried out by the Anatolian Society of Medical Oncology. A total of 178 patients with rectal cancers who underwent curative surgery between January 1994 and August 2012 in 13 centers were included in the study. Patient demographics, including survival data and tumor characteristics were obtained from medical charts. Results: The median age was 58 years (range 26-85 years). Most tumors were well or moderately differentiated. For adjuvant treatment, 13 patients (7.3%) received radiotherapy alone, 12 patients (6.7%) received chemotherapy alone and 15 patients (8.4%) were given chemoradiotherapy. Median follow up was 29 months (3-225 months). Some 42 patients (23.6%) had relapse during follow up; 30 with local recurrence (71.4%) whereas 12 (28.6%) were distant metastases. Among the patients, 5-year DFS was 64% and OS was 82%. Mucinous histology and receiving adjuvant therapy were found to have statistically insignificant correlations with relapse and survival. Conclusions: In our retrospective analysis, approximately one quarter of patients exhibited either local or systemic relapse. The rates of relapse were slightly higher in the patients who had no adjuvant therapy. There may thus be a role for adjuvant therapy in high-risk stage I rectal tumors.
Nirdosh Kumar,Meraj Fatima,Sara Ghaffar,Faysal Subhani,Shahan Waheed 대한응급의학회 2023 Clinical and Experimental Emergency Medicine Vol.10 No.2
Emergency physicians (EPs) working in low-resource settings, where patients mainly bear the cost of healthcare delivery, face many challenges. Emergency care is patient-centered and ethical challenges are numerous in situations where patient autonomy and beneficence are fragile. This review discusses some of the common bioethical issues in the resuscitation and postresuscitation phases of treatment. Solutions are proposed and the necessity for evidence-based ethics and unanimity on ethical standards is emphasized. After a consensus was reached on the structure of the article, smaller groups of authors (2–3) wrote narrative reviews of ethical issues such as patient autonomy and honesty, beneficence and nonmaleficence, dignity, justice, and specific practices and circumstances such as family presence during resuscitation after discussions with senior EPs. Ethical dilemmas were discussed, and solutions were proposed. Cases related to medical decision-making by proxy, financial constraints in management, and resuscitation in the face of medical futility have been discussed. Solutions proposed include the early-stage involvement of hospital ethics committees, financial assurance in place beforehand, and allowing some leverage on a case-to-case basis when care is futile. We recommend developing evidence-based national ethical guidelines and incorporating societal and cultural norms with autonomy, beneficence, nonmaleficence, honesty, and justice principles.
Knockdown of the host cellular protein transportin 3 attenuates prototype foamy virus infection.
Ali, Md Khadem,Kim, Jinsun,Hamid, Faysal Bin,Shin, Cha-Gyun Japan Society for Bioscience, Biotechnology, and A 2015 Bioscience, Biotechnology, and Biochemistry Vol.79 No.6
<P>Transportin 3 (TNPO3) is a member of the importin-s superfamily proteins. Despite numerous studies, the exact molecular mechanism of TNPO3 in retroviral infection is still controversial. Here, we provide evidence for the role and mechanism of TNPO3 in the replication of prototype foamy virus (PFV). Our findings revealed that PFV infection was reduced 2-fold by knockdown (KD) of TNPO3. However, late stage of viral replication including transcription, translation, viral assembly, and release was not influenced. The differential cellular localization of PFV integrase (IN) in KD cells pinpointed a remarkable reduction of viral replication at the nuclear import step. We also found that TNPO3 interacted with PFV IN but not with Gag, suggesting that IN-TNPO3 interaction is important for nuclear import of PFV pre-integration complex. Our report enlightens the mechanism of PFV interaction with TNPO3 and support ongoing research on PFV as a promising safe vector for gene therapy.</P>