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The complexity of the nervous system structure and function, and its slow regeneration rate, makes it more difficult to treat compared to other tissues in the human body when an injury occurs. Moreover, the current therapeutic approaches including the use of autografts, allografts, and pharmacological agents have several drawbacks and can not fully restore nervous system injuries. Recently, nanotechnology and tissue engineering approaches have attracted many researchers to guide tissue regeneration in an effective manner. Owing to their remarkable physicochemical and biological properties, two-dimensional (2D) nanomaterials have been extensively studied in the tissue engineering and regenerative medicine field. The great conductivity of these materials makes them a promising candidate for the development of novel scaffolds for neural tissue engineering application. Moreover, the high loading capacity of 2D nanomaterials also has attracted many researchers to utilize them as a drug/gene delivery method to treat various devastating nervous system disorders. This review will first introduce the fundamental physicochemical properties of 2D nanomaterials used in biomedicine and the supporting biological properties of 2D nanomaterials for inducing neuroregeneration, including their biocompatibility on neural cells, the ability to promote the neural differentiation of stem cells, and their immunomodulatory properties which are beneficial for alleviating chronic inflammation at the site of the nervous system injury. It also discusses various types of 2D nanomaterials-based scaffolds for neural tissue engineering applications. Then, the latest progress on the use of 2D nanomaterials for nervous system disorder treatment is summarized. Finally, a discussion of the challenges and prospects of 2D nanomaterials-based applications in neural tissue engineering is provided.

Large bone defects caused by bone-related diseases and traumatic injuries can disrupt the self-healing potential of bone tissue. Mesenchymal stem cells (MSCs) are known as promising cell sources for bone tissue regeneration. Graphene oxide (GO), a derivative of graphene, has been recently used for controlling the differentiation of stem cells towards bone-forming cells. However, the effect of GO on the intracellular redox system in MSCs is still unknown. In this study, we found that low-dose GO nanosheets (0.1 μg mL-1) did not affect the viability and slightly increased the proliferation of BM-MSCs. Moreover, they could also maintain the redox balance by upregulating the antioxidant genes such as MnSOD and catalase during osteogenic differentiation. The osteoinductive and antioxidative effects of the low-dose GO nanosheets were regulated by the activation and nuclear localization of FoxO1, and its activation was dependent on the JNK activity. The blockade of JNK activity by SP600125 inhibited the nuclear translocation of FoxO1, and subsequently suppressed the osteogenic differentiation and antioxidant defense system of BM-MSCs. Overall, our results show that the osteoinductive and antioxidative effects of low-dose GO nanosheets occur through the activation of the JNK and FoxO1 signaling pathways.

Due to the ability to differentiate into variety of cell types, mesenchymal stem cells (MSCs) hold promise as source in cell-based therapy for treating injured tissue and degenerative diseases. The potential use of MSCs to replace or repair damaged tissues may depend on the efficient differentiation protocols to derive specialized cells without any negative side effects. Identification of appropriate cues that support the lineage-specific differentiation of stem cells is critical for tissue healing and cellular therapy. Recently, a number of stimuli have been utilized to direct the differentiation of stem cells. Biochemical stimuli such as small molecule, growth factor and miRNA have been traditionally used to regulate the fate of stem cells. In recent years, many studies have reported that biophysical stimuli including cyclic mechanical strain, fluid shear stress, microgravity, electrical stimulation, matrix stiffness and topography can also be sensed by stem cells through mechanical receptors, thus affecting the stem cell behaviors including their differentiation potential. In this paper, we review all the most recent literature on the application of biochemical and biophysical cues on regulating MSC differentiation. An extensive literature search was done using electronic database (Medline/Pubmed). Although there are still some challenges that need to be taken into consideration before translating these methods into clinics, biochemical and biophysical stimulation appears to be an attractive method to manipulate the lineage commitment of MSCs.

Angiogenesis, a process of new blood vessel formation from existing blood vessels, plays an important role in tumor growth and the tissue repair process. It is generally acknowledged that angiogenesis might contribute two both processes. In tumor growth, angiogenesis often increases oncogenic signaling, and in tissue repair, it decreases the stiffness of wound tissue and potentially exacerbates scar formation, resulting in pain and poor function. These poor outcomes are due to an increase in the expression of important genes involved in angiogenesis, such as hypoxia-inducible factor-1 alpha (HIF-1α) and its transcriptional target vascular endothelial growth factor (VEGF). Therefore, this adverse effect of angiogenesis should be taken into consideration. Limiting vessel growth instead of boosting growth may be beneficial for favorable long-term healing outcomes. Posttranslational modifications, including acetylation, which is mediated by histone acetyltransferases, and deacetylation, which is mediated by histone deacetylases (HDACs), are critical to HIF-1α function. Most studies have indicated that HDAC inhibitors (HDACIs) show great promise as antiangiogenic agents in the early phase of clinical trials. In this review, we discuss the role of the HDACs HIF-1α and VEGF in angiogenesis. Furthermore, we also discuss the molecular and cellular underpinnings of the effects of HDACIs on antiangiogenesis, which creates new avenues for anticancer therapeutics and the repair of wounded tissue.

One of the most important metabolic hallmarks of cancer cells is deregulation of lipid metabolism. In addition, enhancing de novo fatty acid (FA) synthesis, increasing lipid uptake and lipolysis have also been considered as means of FA acquisition in cancer cells. FAs are involved in various aspects of tumourigenesis and tumour progression. Therefore, targeting lipid metabolism is a promising therapeutic strategy for human cancer. Recent studies have shown that reprogramming lipid metabolism plays important roles in providing energy, macromolecules for membrane synthesis, and lipid signals during cancer progression. Moreover, accumulation of lipid droplets in cancer cells acts as a pivotal adaptive response to harmful conditions. Here, we provide a brief review of the crucial roles of FA metabolism in cancer development, and place emphasis on FA origin, utilization and storage in cancer cells. Understanding the regulation of lipid metabolism in cancer cells has important implications for exploring a new therapeutic strategy for management and treatment of cancer.

Mesenchymal stem cells (MSCs) are multilineage cells with the ability to self-renew and differentiate into a variety of cell types, which play key roles in tissue healing and regenerative medicine. Bone marrow-derived mesenchymal stem cells (BMSCs) are the most frequently used stem cells in cell therapy and tissue engineering. However, it is prerequisite for BMSCs to mobilize from bone marrow and migrate into injured tissues during the healing process, through peripheral circulation. The migration of BMSCs is regulated by mechanical and chemical factors in this trafficking process. In this paper, we review the effects of several main regulatory factors on BMSC migration and its underlying mechanism; discuss two critical roles of BMSCs—namely, directed differentiation and the paracrine function—in tissue repair; and provide insight into the relationship between BMSC migration and tissue repair, which may provide a better guide for clinical applications in tissue repair through the efficient regulation of BMSC migration.

In 2006, the Indonesian Renal Registry (Pernefri) shows about 12,5% of people in Indonesia suffer from chronic kidney disease. The most common cause of chronic kidney disease in 2018 in Indonesia is 39% by renal hypertension and 22% by Diabetic Nephropathy. This cross-sectional study was conducted at "RT" Hospital in Jakarta from 2018 to 2019. The Independent variable in this research was comorbid hypertension and obedience treatment, whereas dependent variables were risk category for kidney deterioration progression and the causal relationship tested with Pearson Chi-Square and Fisher exact as an alternative test. The study included 26 respondents, with 17 (65.4%) patients having hypertension in diabetic nephropathy. Eighty percent of respondents who did not routinely seek treatment in the hypertension group had progression from kidney failure to the Deep Red (Highest Risk) category. Fisher Exact statistical test analysis in the group with a history of comorbidities in the form of hypertension found no significant relationship between non-routine treatment with the progression of chronic kidney failure in the Highest-Very Highest Risk category (p-value = 0.515). Still, a large risk was found in the non-group routine treatment with a chance of 1.33 (0.962 - 1.848) times to have the progression of chronic kidney failure in the category of Highest-Very Highest Risk. Can be concluded that controlling blood pressure and treatment proven to slow worsening kidney function in nephropathy diabetic, even though no significant relationship has been found due to lack of sample. Keywords: diabetic nephropathy; hypertension; prognosis AbstrakPerhimpunan Nefrologi Indonesia (Pernefri) tahun 2006 merilis data penderita gagal ginjal kronis di Indonesia sebesar 12,5%. Etiologi terbesar gagal ginjal kroniks menurut Indonesian Renal Registry tahun 2018 adalah penyakit ginjal hipertensi sebesar 39% dan nefropati diabetic sebesar 22%. Potong lintang pada pasien di RS”RT” Jakarta tahun 2018-2019. Variabel bebas dalam penelitian ini adalah komorbid hipertensi dan kepatuhan berobat, sedangkan variable tergantung dalam penelitian ini berupa kategori risiko progresifitas perburukan ginjal serta hubungan sebab akibat diuji dengan Peason Chi Square dan uji alternatif Fisher Exact Test. Penelitian berlangsung mengikutsertakan 26 responden, dengan prevalensi hipertensi pada pasien nefropati diabetik sebesar 17 (65,4%). Delapan puluh persen responden yang tidak rutin berobat pada kelompok hipertensi memiliki progresifitas penyakit gagal ginjal hingga kategori Deep Red (Highest Risk). Analisa uji statistik Fisher Exact pada kelompok dengan riwayat penyakit penyerta berupa hipertensi didapatkan tidak hubungan yang bermakna antara tidak rutin berobat dengan progresifitas penyakit gagal ginjal kronis kategori Highest-Very Highest Risk (p-value = 0,515) tetapi secara besar risiko didapatkan bahwa kelompok yang tidak rutin berobat memiliki risiko 1,33 (0,962 – 1,848) kali untuk memiliki progresifitas penyakit gagal ginjal kronis kategori Highest-Very Highest Risk. Dapat disimpulkan bahwa engontrol tekanan darah dan rutinitas berobat dapat memperlambat perburukan fungsi ginjal akibat komplikasi lanjut dari nefropati diabetikum, walaupun belum didapatkan hubungan yang bermakan dikarenakan kurangnya besar sampel pada penelitian ini.

Mobilization from the bone marrow and the migration of bone-marrow-derived mesenchymal stem cells (BMSCs) through the peripheral circulation to injured tissue sites are regulated by multiple mechanical and chemical factors. We previously demonstrated that mechanical stretching promotes the migration but inhibits the invasion of BMSCs. However, the involved mechanisms, especially the mechanism of stretching-inhibited BMSC invasion, have not been thoroughly elucidated to date. In this study, we found that mechanical stretching with a 10% amplitude at a 1-Hz frequency for 8 hr significantly reduces BMSC invasion and downregulates the expression of membrane type-1 matrix metalloproteinases (MT1-MMP) at both the messenger RNA and protein levels. The overexpression of MT1-MMP restores mechanical stretching-reduced BMSC invasion. Moreover, phosphatidylinositol 3-kinase (PI3K)-dependent Akt phosphorylation in BMSCs was found to be inactivated by mechanical stretching. Pharmacological inhibitors of PI3K/Akt signaling (LY294002 or A443654) reduced the expression of MT1-MMP and impaired BMSC invasion. In addition, the upregulation of Akt phosphorylation by a pharmacological activator (SC79) increased MT1-MMP expression and suppressed mechanical stretching-reduced BMSC invasion. Taken together, our results suggest that mechanical stretching inhibits BMSC invasion by downregulating MT1-MMP expression by suppressing the PI3K/Akt signaling pathway.

Background Tendon is composed of connective tissue, is able to retract with high tensile force, and plays a significant role in musculoskeletal motion. However, inappropriate physical training or accidents often result in tendon injuries. So far, the functional healing of injured tendon is still a great challenge in orthopedics. Mesenchymal stem cells (MSCs) are multilineage cells with the ability to self-renew and differentiate into a variety of cell types, including tenocytes. The plasticity of MSCs gives rise to the chance of improved healing of injured tendons and even tissue-engineered tendons. Recently, more and more works have shown that the paracrine mechanisms of MSCs also play a critical role in driving the tendon repair process. Objective The purpose of this review is to summarize the current knowledge of the induction of tenogenic differentiation of MSCs by mechanical, chemical and mechanochemical stimulations. The role of paracrine mechanisms of MSCs during the repair of injured tendons is also discussed. Conclusion The multilineage potential and the paracrine effects of MSCs create the chance for improved healing of injured tendons and even tissue-engineered tendons. The understanding of the regulation of the two different repair mechanisms (directed differentiation and paracrine) of MSCs has important implications for tendon repair and regeneration.