Electrochemical Fe-catalysed radical cyclization for the synthesis of oxindoles.

We report an efficient and sustainable electrocatalytic approach for the synthesis of 3,3-disubstituted 2-oxindoles bearing ester groups from readily accessible N-arylacrylamides and carbazates. The reaction proceeds through an electrochemical iron-catalyzed radical addition/cyclization sequence with a commercially available iron catalyst and carbazates as alkoxycarbonyl radical precursors. This mild and operationally simple method transforms a wide range of structurally diverse N-arylacrylamides into oxindole derivatives in good yields and can be smoothly scaled up for the preparation of synthetically valuable oxindoles that are key intermediates for the synthesis of natural products.

Jade material in vitro and in vivo: A study on the anti-inflammatory and repair efficacy of jade material on the skin.

OBJECTIVE: The biological safety of natural jade materials and assembled jade-activated materials on cells and their anti-inflammatory and damage repair functions, as well as the repair function on sensitive skin, were studied utilizing in vitro cell biology and in vivo. METHODS: Human skin fibroblasts were used as model cells to conduct cytotoxicity experiments in vitro, and the effects on the expression of inflammatory factors and growth factor-related genes in fibroblasts were explored. The gene expression values of inflammatory factors IL-1, IL-6, TNF-α and cytokines epidermal growth factors, fibroblast growth factors and COL1A1 in fibroblasts were measured by polymerase chain reaction test. Thirty women with sensitive skin were selected to apply a mask containing jade extract three times a week. After two weeks, non-invasive measures related to skin sensitivity were tested. RESULTS: We confirmed the presence of anti-inflammatory effects in both jade materials, with the effects of the assembled activated jade material being superior to that of the natural jade material. Jade extracts significantly increased the gene expressions of EGF, FGF and COL1A1 in HDF. The results of the in vivo study showed that the mask containing jade extract could significantly increase the skin hydration and decrease the rate of transepidermal water loss and skin lactic acid sting test scores after two weeks of use. Subjective evaluations confirmed improvements in skin dryness, smoothness and fineness. No new sensitization occurred in subjects, and the product was non-irritating. No adverse skin reactions were observed during the test. CONCLUSIONS: The jade materials were able to downregulate the expression of inflammatory factor genes, up-regulate the expression of growth factor genes, and improve the anti-inflammation and repair ability of skin. Furthermore, the test results of participants with sensitive skin after using the mask containing jade extract showed that the mask has repairing ability.

OBJECTIF: L'innocuité du jade naturel, et des substances assemblées activées par le jade, sur les cellules, leurs effets anti-inflammatoire et réparateur, ainsi que leur action réparatrice sur les peaux sensibles ont été étudiés au moyen de la biologie cellulaire in vitro et in vivo. MÉTHODES: Des fibroblastes de peau humaine (HDF - Human Dermal Fibrolasts) ont été utilisés comme cellules modèles pour réaliser des tests de cytotoxicité in vitro, et les effets sur l'expression des facteurs inflammatoires et des gènes associés aux facteurs de croissance dans les fibroblastes ont été étudiés. Les valeurs de l'expression génique des facteurs inflammatoires IL-1, IL-6, TNF-α, des facteurs de croissance épidermique des cytokines (EGF - Epidermal Growth Factor), des facteurs de croissance des fibroblastes (FGF - Fibroblast Growth Factor), et du COL1A1 (Gène Collagen, type I, alpha 1) dans les fibroblastes ont été mesurées au moyen d'un test de réaction en chaîne par polymérase. Trente femmes présentant une peau sensible ont été sélectionnées pour appliquer un masque contenant de l'extrait de jade trois fois par semaine. Au bout de deux semaines, des mesures non invasives de la sensibilité de la peau ont été réalisées. RÉSULTATS: Nous confirmons la présence d'effets anti-inflammatoires pour les deux substances, avec de meilleurs résultats pour la substance assemblée activée par le jade comparé à ceux du jade naturel. Les extraits de jade ont significativement augmenté l'expression de l'EGF, du FGF, et du COL1A1 dans les HDF. Les résultats de l'étude in vivo ont révélé que le masque contenant de l'extrait de jade pouvait améliorer significativement l'hydratation de la peau, réduire le pourcentage de perte en eau trans-épidermique et améliorer les résultats du test de piqûre d'acide lactique (LAST - Lactic Acid Sting Test) de la peau après deux semaines d'utilisation. Les évaluations subjectives ont confirmé des améliorations de la sécheresse cutanée, de la douceur et de la finesse du grain de la peau. Aucune nouvelle sensibilisation n'est apparue chez les sujets, et le produit s'est avéré non-irritant. De même, aucune réaction cutanée indésirable n'a été observée pendant le test. CONCLUSIONS: Le jade a été capable de réguler à la baisse l'expression des gènes associés aux facteurs inflammatoires, de réguler à la hausse l'expression des gènes associés aux facteurs de croissance, et d'améliorer les capacités anti-inflammatoire et réparatrice de la peau. De plus, après utilisation du masque contenant de l'extrait de jade, les résultats des tests chez les participantes ayant une peau sensible ont démontré que ce masque avait une capacité réparatrice.

Multiple Genetic Mutations Related to Insecticide Resistance are Detected in Field Kazakhstani House Flies (Muscidae: Diptera).

The house fly (Musca domestica Linnaeus) is an important disease vector. Insecticide resistance is an obstacle to effective house fly control. Previous studies have demonstrated that point mutations in acetylcholinesterase (Ace), carboxylesterase (MdαE7) and voltage-sensitive sodium channel (Vssc), and over-expression of CYP6D1v1 confer insecticide resistance in the house fly. However, information about the status and underlying mechanisms of insecticide resistance in Kazakhstani house flies is lacking. In this study, we investigated the occurrence of genetic mutations associated with insecticide resistance in field house flies collected at six different locations in southern Kazakhstan. Four mutations (V260L, G342A/V, and F407Y) in Ace and three mutations (G137D and W251L/S) in MdαE7 were detected with appreciable frequencies. Notably, haplotypes carrying triple-loci mutations in Ace and double mutations in MdαE7 were found in Kazakhstan. The L1014H and L1014F mutations in Vssc, and CYP6D1v1 resistance allele were detected at a low frequency in some of the six investigated house fly populations. Phylogenetic analyses of haplotypes supported multiple origins of resistance mutations in Ace and MdαE7. These observations suggest that house flies in southern Kazakhstan may exhibit significant resistance to organophosphates and carbamates. Regular monitoring of insecticide resistance is recommended to achieve effective house fly control by chemical agents in southern Kazakhstan.

Human umbilical cord mesenchymal stem cells transplantation improves cognitive function in Alzheimer's disease mice by decreasing oxidative stress and promoting hippocampal neurogenesis.

Stem cell transplantation represents a promising therapy for central nervous system injuries, but its application to Alzheimer's disease (AD) is still limited and the potential mechanism for cognition improvement remains to be elucidated. In the present study, we used Tg2576 mice which express AD-like pathological forms of amyloid precursor protein (APP) to investigate the effects of human umbilical cord mesenchymal stem cells (hUC-MSCs) intravenous transplantation on AD mice. Interestingly, hUC-MSCs transplantation significantly ameliorated cognitive function of AD mice without altering Aß levels in hippocampus. Remarkably, hUC-MSCs transplantation reduced oxidative stress in hippocampus of AD mice by decreasing the level of malondialdehyde (MDA), increasing the level of nitric oxide (NO), enhancing the activity of superoxide dismutase (SOD) and neuronal nitric oxide synthase (nNOS). The mechanisms underlying the improved cognitive function may be linked to hippocampal neurogenesis and an up-regulation of neuronal synaptic plasticity related proteins levels including silent information regulator 1 (Sirt1), brain-derived neurotrophic factor (BDNF) and synaptophysin (SYN). Taken together, our findings suggest that hUC-MSCs can improve cognition of AD mice by decreasing oxidative stress and promoting hippocampal neurogenesis. These results suggest that modulating hUC-MSCs to generate excess neuroprotective factors could provide a viable therapy to treat AD.

Wharton's Jelly Transplantation Improves Neurologic Function in a Rat Model of Traumatic Brain Injury.

Traumatic brain injury (TBI), which can lead to disability, dysfunction, and even death, is a prominent health problem worldwide. Effective therapy for this serious and debilitating condition is needed. Human umbilical cord matrix, known as Wharton's jelly (WJ), provides a natural, interface scaffold that is enriched in mesenchymal stem cells. In this study, we tested the efficacy of WJ tissue transplantation in a weight-drop model of TBI in rats. WJ tissue was cultured and transplanted into the injury site 24 h after TBI. The modified neurologic severity score, body weight, brain edema, and lesion volume were evaluated at various time points after TBI. Cognitive behavior was assessed by the novel object recognition test and the Morris water maze test. Expression of brain-derived neurotrophic factor (BDNF) in the perilesional brain area was measured at day 14 after TBI. We found that WJ tissue transplantation lessened TBI-induced brain edema (day 3), reduced lesion volume (day 28), improved neurologic function (days 21-28), and promoted memory and cognitive recovery. Additionally, expression of BDNF mRNA and protein was higher in WJ tissue-treated rats than in sham-operated or vehicle-treated rats. These data suggest that WJ tissue transplantation can reduce TBI-induced brain injury and may have therapeutic potential for the treatment of TBI.