Age-related biological alterations in brain function increase the risk of mild cognitive impairment and dementia, a global problem exacerbated by aging populations in developed nations. Limited pharmacological therapies have resulted in attention turning to the promising role of medicinal plants and dietary supplements in the treatment and prevention of dementia. Sugarcane (Saccharum officinarum L.) top, largely considered as a by-product because of its low sugar content, in fact contains the most abundant amounts of antioxidant polyphenols relative to the rest of the plant. Given the numerous epidemiological studies on the effects of polyphenols on cognitive function, in this study, we analyzed polyphenolic constituents of sugarcane top and examined the effect of sugarcane top ethanolic extract (STEE) on a range of central nervous system functions in vitro and in vivo. Orally administrated STEE rescued spatial learning and memory deficit in the senescence-accelerated mouse prone 8 (SAMP8) mice, a non-transgeeural stem cells (hNSCs), regulated bHLH factor expression and induced neuronal differentiation and astrocytic process lengthening. Altogether, our findings suggest the potential of STEE as a dietary intervention, with promising implications as a novel nutraceutical for cognitive health.
Cerebral ischemic injury is a complicated pathological process. Adipose-derived stromal cells (ADSCs) have been used as a therapeutic strategy, with their therapeutic effects chiefly attributed to paracrine action rather than
differentiation. Studies have shown that circAkap7 was found to be downregulated in a mouse model of transient middle cerebral artery occlusion (tMCAO).

To explore whether exosomes derived from circAkap7-modified ADSCs (exo-circAkap7) have therapeutic effects on cerebral ischemic injury, a mouse model of tMCAO, as well as an
model of oxygen and glucose deprivation-reoxygenation (OGD-R) in primary astrocytes, were used.

Results showed that treatment with exo-circAkap7 protected against tMCAO in mice, and
experiments confirmed that co-culture with exo-circAkap7 attenuated OGD-R-induced cellular injury by absorbing miR-155-5p, promoting ATG12-mediated autophagy, and inhibiting NRF2-mediated oxidative stress.

We demonstrate here that exo-circAkap7 protected against cerebral ischemic injury by promoting autophagy and ameliorating oxidative stress.
We demonstrate here that exo-circAkap7 protected against cerebral ischemic injury by promoting autophagy and ameliorating oxidative stress.Glucose-6-phosphate dehydrogenase (G6PDH) is the rate-limiting enzyme in the pentose phosphate pathway (PPP) and plays a crucial role in the maintenance of redox homeostasis by producing nicotinamide adenine dinucleotide phosphate (NADPH), the major intracellular reductant. G6PDH has been shown to be a biomarker and potential therapeutic target for renal cell carcinoma (RCC). Here, we report a previously unknown biochemical mechanism through which caffeine, a well-known natural small molecule, regulates G6PDH activity to disrupt cellular redox homeostasis and suppress RCC development and progression. We found that caffeine can inhibit G6PDH enzymatic activity. Mechanistically, caffeine directly binds to G6PDH with high affinity (KD = 0.1923 μM) and competes with the coenzyme NADP+ for G6PDH binding, as demonstrated by the decreased binding affinities of G6PDH for its coenzyme and substrate. Molecular docking studies revealed that caffeine binds to G6PDH at the structural NADP+ binding site, and chemical cross-linking analysis demonstrated that caffeine inhibits the formation of dimeric G6PDH. G6PDH inhibition abrogated the inhibitory effects of caffeine on RCC cell growth. Moreover, inhibition of G6PDH activity by caffeine led to a reduction in the intracellular levels of NADPH and reactive oxygen species (ROS), and altered the expression of redox-related proteins in RCC cells. Accordingly, caffeine could inhibit tumor growth through inhibition of G6PDH activity in vivo. Taken together, these results demonstrated that caffeine can target G6PDH to disrupt redox homeostasis and inhibit RCC tumor growth, and has potential as a therapeutic agent for the treatment of RCC.The ongoing COVID-19 pandemic still requires fast and effective efforts from all fronts, including epidemiology, clinical practice, molecular medicine, and pharmacology. A comprehensive molecular framework of the disease is needed to better understand its pathological mechanisms, and to design successful treatments able to slow down and stop the impressive pace of the outbreak and harsh clinical symptomatology, possibly via the use of readily available, off-the-shelf drugs. This work engages in providing a wider picture of the human molecular landscape of the SARS-CoV-2 infection via a network medicine approach as the ground for a drug repurposing strategy. Grounding on prior knowledge such as experimentally validated host proteins known to be viral interactors, tissue-specific gene expression data, and using network analysis techniques such as network propagation and connectivity significance, the host molecular reaction network to the viral invasion is explored and exploited to infer and prioritize candidate target genes, and finally to propose drugs to be repurposed for the treatment of COVID-19. Ranks of potential target genes have been obtained for coherent groups of tissues/organs, potential and distinct sites of interaction between the virus and the organism. click here The normalization and the aggregation of the different scores allowed to define a preliminary, restricted list of genes candidates as pharmacological targets for drug repurposing, with the aim of contrasting different phases of the virus infection and viral replication cycle.
Retinoblastoma (RB) is a potentially heritable childhood cancer that is vision- and life-threatening. Assessing the risk of inheriting RB is important for structuring ophthalmic and genetic screening of family members.

To create a free online application that integrates phenotypic, genetic, and familial relationships with clinical best practice surveillance guidelines for families with RB.

The risk of germline
gene mutation was assessed for first- and second-degree relatives of a proband under variable clinical scenarios, integrating age, phenotype, relationship data, and genotype (germline
mutation status detected, undetected, not tested). Based on the assessed risk of a germline
mutation, recommendations regarding further genetic testing as well as ophthalmic surveillance were derived from consensus guidelines.

The recommendations depend on the
germline mutation status (detected, undetected, not tested), which were further subcategorized by the results of tumor phenotype, relationship to proband, age of the relative, and family structure.click here