Cryopreserved clinical-grade human embryonic stem cell-derived dopaminergic progenitors function in Parkinson's disease models.

AIM: Parkinson's Disease (PD) is a common age-related neurodegenerative disorder with a rising prevalence. Human pluripotent stem cells have emerged as the most promising source of cells for midbrain dopaminergic (mDA) neuron replacement in PD. This study aimed to generate transplantable mDA progenitors for treatment of PD. MATERIALS AND METHODS: Here, we optimized and fine-tuned a differentiation protocol using a combination of small molecules and growth factors to induce mDA progenitors to comply with good manufacturing practice (GMP) guidelines based on our clinical-grade human embryonic stem cell (hESC) line. KEY FINDINGS: The resulting mDA progenitors demonstrated robust differentiation and functional properties in vitro. Moreover, cryopreserved mDA progenitors were transplanted into 6-hydroxydopamine-lesioned rats, leading to functional recovery. SIGNIFICANCE: We demonstrate that our optimized protocol using a clinical hESC line is suitable for generating clinical-grade mDA progenitors and provides the ground work for future translational applications.

Involvement of IGF/IGFBP/Erk axis in the exercise-mediated preventive effects on colorectal cancer in rats.

Recent studies have indicated that downregulation of insulin-like growth factor (IGF)-1 and its downstream targets are the main mechanisms underlying the anti-cancer impact of exercise. Therefore, we examined the impact of exercise on chemically induced-aberrant crypt foci (ACF), the earliest step of colorectal carcinogenesis, in rats and involvement of the IGF-1/IGF binding protein (IGFBP)-3/Erk axis. Twenty-four male Wistar rats were assigned into two groups (n=12): the control and exercise group. After eight weeks of training intervention, 6 rats were randomly selected from each group and received four injections of 1,2-dimethylhydrazine (DMH; 40 mg/kg), for two weeks. 0.2% methylene blue staining was used to evaluate the number of ACF in the colon. IGF-1 and IGFBP-3 protein levels in the serum were measured using commercially available ELISA kits for rat. The expression levels of proliferating cell nuclear antigen (PCNA), Erk1/2 and p-Erk1/2 were evaluated in colon tissue. Histological assessments were also performed in all groups. We found that the total number of ACF was significantly lowered after eight-week exercise (P<0.05). Moreover, the exercise program downregulated the IGF-1, PCNA, and p-Erk1/2 expressions and upregulated IGFBP-3 expression. Exercise was also found to increase the goblet cell number and improved colon architecture. Our finding demonstrated reduced ACF number in rat colons following exercise training, and this function may be associated with the inhibition of IGF-1/IGFBP-3/Erk1/2 signaling. Therefore, exercise appears to result in a lower number of ACF for preventing colon cancer.

Optogenetics in the Era of Cerebral Organoids.

The human brain has been deemed the most complex organ and has captivated neuroscientists for decades. Most studies of this organ have relied on reductionist model systems. Although all model systems are essentially wrong, cerebral organoids so far represent the closest recapitulation of human brain development and disease both in terms of cell diversity and organization. The optogenetic technique can be used in this context to study the functional neuroanatomy of the brain, to examine the neural circuits, and to determine the etiology of neurological disorders. In this opinion article, we suggest ways in which optogenetics can be combined with cerebral organoids to allow unprecedented precision and accuracy in studying normal and aberrant neurodevelopmental processes and, as well, neurodegenerative diseases.

Quercetin: A functional dietary flavonoid with potential chemo-preventive properties in colorectal cancer.

Recently, an intense attention has been paid to the application of natural compounds as a novel therapeutic strategy for cancer treatment. Quercetin, a natural flavonol present in many commonly consumed food items, is widely demonstrated to exert inhibitory effects on cancer progression through various mechanisms. Since there is a strong association with diets containing abundant vegetables, fruits, and grains, and significant decline in the risk of colon cancer, accumulation studies have focused on the anticancer potential of quercetin in colorectal cancer. Cell cycle arrest, increase in apoptosis, antioxidant replication, modulation of estrogen receptors, regulation of signaling pathways, inhibition of and metastasis and angiogenesis are among various mechanisms underlying the chemo-preventive effects of quercetin in colorectal cancer. This review covers various therapeutic interactions of Quercetin as to how targets cellular involved in cancer treatment.

Physiological responses to cadmium stress in strawberry treated with pomegranate peel-activated carbon.

Many reports have already been published regarding the removal of heavy metals from aqueous solutions onto activated carbon. However, the biosorbents' effect on the plant response still needs further investigation. In this study, activated carbon derived from the pomegranate peel [pomegranate activated carbons (PAC)] was used to see the effects of the addition of PAC on growing strawberry in Cd-contaminated sand. Cd accumulation and toxicity to strawberry was investigated by measuring the concentration of Cd in plant tissues and various biochemical activities of plant. Our results suggested that PAC had a high sorption capacity for Cd. Strawberry plant tried to deal with the Cd-induced oxidative stress by strengthening its antioxidant competences and decreasing Cd absorption. In comparison with the control, PAC applied to the sand decreased the level of lipid peroxidation and enhanced the carotenoid content. The greater tolerance of strawberry toward the level of Cd due to the application of PAC was associated with improving the physical conditions of the soil, increasing the amounts of some essential elements and decreasing the level of Cd absorption. Gaviota strawberry cultivar exposed to 5 or 10 mg kg-1 Cd was able to adopt a new metabolic equilibrium, allowing the plant to cope with this metal.

In vitro histological investigation of interactions between rat decellularized large intestine scaffold and human adipose derived mesenchymal stem cells.

The aim of this study was to investigate the interactions between rat intestine decellularized scaffold and human adipose derived mesenchymal stem cells. Rat large intestine was dissected in fragments and decellularized by physicochemical methods. The scaffolds were loaded by human adipose derived mesenchymal stem cells expressing green fluorescent protein. Microscopic sections were prepared from the scaffolds after two weeks of culture with stem cells and studied by histological methods. The interactions of scaffolds with MSCs were also studied by electron microscopy. Histological and electron microscopy studies revealed human mesenchymal stem cell adhesion, migration, division and maintenance during the 14 days of culture in vitro. According to the results, scaffolds prepared from rat intestine matrix could be a suitable scaffold for studying in vitro cell behaviors such as division, migration and attachment. These various behaviors of cultured cells might be due to inductive effects of the extracellular matrix derived scaffold. However, more investigations are required to discover the exact effects of this scaffold and its interactions with mesenchymal stem cells.

Three-dimensional scaffold from decellularized human gingiva for cell cultures: glycoconjugates and cell behavior.

OBJECTIVE: We studied both the presence of some carbohydrate compounds in a threedimensional (3D) matrix harvested from human gingiva and the cell behavior in this matrix. MATERIALS AND METHODS: In this experimental research, in order to prepare 3D scaffolds, human palatal gingival biopsies were harvested and physically decellularized by freezethawing and sodium dodecyl sulfate (SDS). The scaffolds were placed within the rings of blastema tissues obtained from a pinna rabbit, in vitro. We evaluated the presence of glycoconjugatesand cellular behavior according to histological, histochemical and spectrophotometry techniques at one, two and three weeks after culture. One-way analysis of variance (ANOVA)comparedthe groups. RESULTS: Extracellular matrix (ECM) remained after decellularization of tissue with 1% SDS. Glycoconjugate contents decreased meaningfully at a higher SDS concentration (p<0.0001). After culture of the ECM scaffold with blastema, we observed increased staining of alcian blue, periodic acid-Schiff (PAS) and toluidine blue in the scaffold and a number of other migrant cells which was caused by cell penetrationinto the scaffold. Spectrophotometry results showed an increase in glycosaminoglycans (GAGs) of the decellularized scaffolds at three weeks after culture. CONCLUSION: The present study has shown that a scaffold generated from palatal gingival tissue ECM is a suitable substrate for blastema cell migration and activity.This scaffold maypotentially be useful as a biological scaffold in tissue engineering applications.