Mediha Canbek

Karaciğer rejenerasyonu çok sayıda kompleksin görev aldığı karmaşık bir mekanizmadır. Rejenerasyon, karaciğerin %70’nin çıkarılmasıyla tetiklenir ve hücreler, 1-2 bölünmeden sonra tekrar G0 fazına geçer. Karaciğer rejenerasyonu sırasında mitokondrilerin şekilsel olarak bozulduğu, krista sayının arttığı, şiştiği ancak; ilerleyen saatlerde normale döndüğü bilinmektedir. Karaciğer rejenerasyonu sırasında mitokondrilerin nasıl normale döndüğü ile ilgili moleküler mekanizmalar açık değildir. Mitokondrilerin, günümüzde, enerji üretimi dışında farklı mekanizmalarla (mitofaji, mitokondriyal fizyon, kalsiyum homeostazisi Fe-S protein sentezi gibi) ilişkisi açıktır. Bu nedenle çalışmamızda parsiyal hepatektomi ile tetiklenen karaciğer rejenerasyonunda Drp1 gen ekspresyonu ve DRP1, MUL1 protein miktarları belirlenerek MUL1 aracılı mitofaji/mitokondriyal fizyon mekanizmasının olası aktivasyonu rejenerasyonun 6, 12, 24 saatlerine göre değerlendirilmiştir. Elde edilen veriler sonucunda; MUL1 protein miktarlarında; PH rejenerasyon gruplarında, Sham gruplarına göre düşüş olduğu belirlenmiştir. Drp1 değerlendirildiğinde genel olarak PH gruplarında düşmesine rağmen PH12. saatte meydana gelen hafif artış ilginçtir. Drp1 ekspresyonu ve protein miktarındaki bu artışın mitofajiden ziyade farklı mekanizmalarla (Kalsiyum homeostazı, ERAD) ilişkili olabileceğini düşündürüyor. Bunun için daha fazla araştırmaya ihtiyaç vardır.

Background: Cartilage injuries are currently the most prevalent joint disease. Previous studies have emphasized the use of stem cells as the effective treatment for regenerating cartilage damage. Objective: In this study, considering the difficulties of the cellular therapy method, it was hypothesized that human synovial fluid-derived mesenchymal stem cell (hSFMSC) exosomes as a SC source could be used to treat these injuries as a safer and cell-free therapeutic alternative procedure due to its direct relevance to cartilage regeneration. Moreover, this study aimed to determine the miRNA and target genes required for the formation of SC treatment combined with gene therapy in order to reveal the mechanism of cartilage regeneration and increase its effectiveness. Methods: MSCs were characterized by flow cytometry, and immunocytochemical and differentiation analyses were done. To characterize functionally isolated exosomes, in vitro uptake analysis was performed. RT-qPCR was used to examine in terms of the advantages of cellular and cell-free therapy, mature human chondroblasts derived by differentiation from hSF-MSCs and human chondrocyte profiles were compared in order to demonstrate the above profile of hSF-MSCs and exosomes isolated from them, and the effectiveness of SC therapy in repairing cartilage damage. Results: According to our findings, the expression level of hsa-miR-155-5p was found to be considerably higher in chondrocytes differentiated from human synovial fluid MSCs than in mature human chondrocytes. These findings were also supported by the TGF-signalling pathway and chondrogenesis marker genes. Conclusion: It was concluded that hSF-MSCs and exosomes can be used in the treatment of cartilage damage, and hsa-miR-155-5p can be used as a target miRNA in a new gene therapy approach because it increases the therapeutic effect on cartilage damage.

The life expectancy of the naked mole-rat (Heterocephalus glaber) is longer than that of other rodents. In NMR cells, the hyaluronic acid concentration is at a higher level. The extracellular matrix’s primary constituent is hyaluronic acid, and CD44 and RHMM are the receptors for hyaluronic acid in the cells. Hyaluronan synthases (HAS); HAS1, HAS2, and HAS3 are located in the plasma membrane and produce hyaluronic acid. Moreover, there are six types of hyaluronic degradation enzymes (Hyal-1, Hyal-2, Hyal-3, Hyal-4, and PH-20). Hyaluronic acid is known to have anti-cancerous effects and acts as a double-edged sword promoting cell senescence and protecting against cellular aging at the same time. NMR’s lengthy lifespan may probably be due to the high molecular weight of hyaluronic acid. INK4 isoforms (P16ink4a/b and pALTINK4a/b) and p27kip1 conferring on NMR a 2-way (early and regular respectively) defense mechanism make NMR more resistant to cancer cells than, humans and mice with only regular contact inhibition (regular (p27kip1). This study, therefore, aims to examine the existing molecular interactions within the NMR-HA-CD44 axis and the ability to confer cancer resistance to mammalian cells through INK4 isoforms gene transfer using the CRISPR method. A lot of potential thus exists in studying these relationships and the prospects for answering the yet unknowns in this area.

Possible protective effects of geraniol, known as antioxidant properties, were analyzed biochemically and histologically on experimental long-term renal ischemia/reperfusion I/R injury in rats. This study used 3-4 months old male Wistar albino rats and were divided into 4 groups (n = 7) by random selection: Group I (Sham Group), Group II (I/R+SF), Group III (I/R+50 mg/kg geraniol), and Group IV (I/R+100 mg/kg geraniol). A right nephrectomy was performed in all groups under anesthesia. Groups I and II were inoculated with SF (1 ml/kg) and Groups III and IV were inoculated with 50 mg/kg and 100 mg/kg of geraniol, injected intraperitoneally. For Groups II, III, and IV, I/R durations were determined to be 60 mins ischemia and 24 hours reperfusion. At the end of the experiment, Urea (BUN), Creatinine (CRE) activities in the blood serum and the catalase (CAT), glutathione peroxidase (GPx) and Superoxide dismutases (SOD), enzyme activities in kidney tissue were measured. Histologic sections were examined by light microscopy using Hematoxylin & Eosine. As a result, it was determined that 100 mg / kg geraniol against renal I/R injury shows more antioxidant effect and protection than 50 mg / kg geraniol.

Geraniol is a monoterpenoid alcohol that has a hepatoprotective effect. We investigated the regenerative effects of geraniol in rats after a 70% partial hepatectomy (PH). Using Wistar albino rats, nine groups were created: Group I was the control group, while the remaining groups received a single intraperitoneal dose of saline, Silymarin, or geraniol after PH. A 70% PH was performed on all groups except for groups II and III. Blood serum samples were obtained for alanine amino transferase (ALT) analysis. Then liver tissues were harvested for histological and real-time polymerase chain reaction (PCR) analyses. Tumor necrosis factor-α (TNFα) and interleukin 6 (IL6) gene expression were examined 24 and 48 h after PH. ALT levels were found to be statistically significantly increased in all PH-treated groups. TNFα and IL6 gene expression levels were elevated in geraniol-treated groups. Histological evaluation revealed a hepatoprotective effect for geraniol-treated groups. Our results suggest that geraniol plays a significant role during liver regeneration, which involves the elevated expression of TNFα and IL6 48 h after PH.

Context • Nuclear factor kB (NF-κB) is a dimeric transcription factor that is involved in the regulation of regenerative and apoptosic genes and plays a key role in liver regeneration after a partial hepatectomy (PH). Complementary medicine is used to treat various diseases and can be obtained from a large number of plants that are found in nature. One such plant is geraniol, and no studies have yet occurred assessing its in vivo effects on liver regeneration. Objective • The current study intended to assess the effects of geraniol on liver regeneration after a 70% PH in rats. Design • The research team studied geraniol in a rat model in vivo. Setting • The study took place in the medical and surgical experimental research center at Eskisehir Osmangazi University (Eskisehir, Turkey). Animals • The animals were Wistar albino male rats. Intervention • The rats were divided into 8 groups with 6 rats in each group. Two groups were the sham control groups. The other 6 groups received an injection of a single dose of saline, the negative control; silymarin, the negative control; or geraniol, the intervention. The injections were given intraperitoneally immediately after PH. A laparotomy was performed on the rats all of those groups at either 24 h or 48 h after the PH. Outcome Measures • Using the reverse transcription (RT)- polymerase chain reaction (PCR) method (RT-PCR) and Western blot analysis, the NF-κB, tumor necrosis factor α, and interleukin 6 gene expression and protein levels were measured. Moreover, the levels of the heat shock proteins (HSPs) HSP27 and HSP60 were examined by Western blot. Results • The data showed that geraniol had a significant role (P < .05) in increasing the process of liver regeneration when given intraperitoneally, and it protected the liver as assessed by histology and the HSP levels. In rats receiving 100 mg/kg geraniol intraperitoneally, the agent induced hepatic regeneration 24 h and 48 h after PH (70%).