Sex Differences In Immune Checkpoint Therapy

Women seem to do better than men in immune checkpoint therapy for cancer.  Studying such differences may help devise improved therapeutic approaches for all patients.  Thus - “The pooled overall survival HR was 0·72 (95% CI 0·65-0·79) in male patients treated with immune checkpoint inhibitors, compared with men treated in control groups. In women treated with immune checkpoint inhibitors, the pooled overall survival HR compared with control groups was 0·86 (95% CI 0·79-0·93). The difference in efficacy between men and women treated with immune checkpoint inhibitors was significant (p=0·0019).’

Tea Genetics

Understanding the tea genome; abstract

Tea, one of the world's most important beverage crops, provides numerous secondary metabolites that account for its rich taste and health benefits. Here we present a high-quality sequence of the genome of tea, Camellia sinensis var. sinensis (CSS), using both Illumina and PacBio sequencing technologies. At least 64% of the 3.1-Gb genome assembly consists of repetitive sequences, and the rest yields 33,932 high-confidence predictions of encoded proteins. Divergence between two major lineages, CSS and Camellia sinensis var. assamica (CSA), is calculated to ∼0.38 to 1.54 million years ago (Mya). Analysis of genic collinearity reveals that the tea genome is the product of two rounds of whole-genome duplications (WGDs) that occurred ∼30 to 40 and ∼90 to 100 Mya. We provide evidence that these WGD events, and subsequent paralogous duplications, had major impacts on the copy numbers of secondary metabolite genes, particularly genes critical to producing three key quality compounds: catechins, theanine, and caffeine. Analyses of transcriptome and phytochemistry data show that amplification and transcriptional divergence of genes encoding a large acyltransferase family and leucoanthocyanidin reductases are associated with the characteristic young leaf accumulation of monomeric galloylated catechins in tea, while functional divergence of a single member of the glutamine synthetase gene family yielded theanine synthetase. This genome sequence will facilitate understanding of tea genome evolution and tea metabolite pathways, and will promote germplasm utilization for breeding improved tea varieties.

Fiber And Microbiota

Dietary fiber can increase levels of certain gut microbiota bacterial species, as well as higher levels of butyrate, a short chain fatty acid with beneficial anti-cancer effects in the colon.  Abstract:

BACKGROUND:

Dysfunction of the gut microbiota is frequently reported as a manifestation of chronic diseases, and therefore presents as a modifiable risk factor in their development. Diet is a major regulator of the gut microbiota and certain types of dietary fiber may modify bacterial numbers and metabolism, including short-chain fatty acid (SCFA) generation.

OBJECTIVE:

A systematic review and meta-analysis were undertaken to assess the effect of dietary fiber interventions on gut microbiota composition in healthy adults.

DESIGN:

A systematic search was conducted across MEDLINE, EMBASE, CENTRAL, and CINAHL for randomized controlled trials using culture and/or molecular microbiological techniques evaluating the effect of fiber intervention on gut microbiota composition in healthy adults. Meta-analyses via a random-effects model were performed on alpha diversity, prespecified bacterial abundances including Bifidobacterium and Lactobacillus spp., and fecal SCFA concentrations comparing dietary fiber interventions with placebo/low-fiber comparators.

RESULTS:

A total of 64 studies involving 2099 participants were included. Dietary fiber intervention resulted in higher abundance of Bifidobacterium spp. [standardized mean difference (SMD) 0.64 (95% CI: 0.42, 0.86); P < 0.00001)] and Lactobacillus spp. [SMD: 0.22 (0.03, 0.41), P = 0.02] as well as fecal butyrate concentration [SMD: 0.24 (0.00, 0.47), P = 0.05] compared with placebo/low-fiber comparators. Subgroup analysis revealed that fructans and galacto-oligosaccharides led to significantly greater abundance of both Bifidobacterium spp. and Lactobacillus spp. compared with comparators (P < 0.00001 and P = 0.002, respectively). No differences in effect were found between fiber intervention and comparators for α-diversity, abundances of other prespecified bacteria, or other SCFA concentrations.

CONCLUSIONS:

Dietary fiber intervention, particularly involving fructans and galacto-oligosaccharides, leads to higher fecal abundance of Bifidobacterium and Lactobacillus spp. but does not affect α-diversity. Further research is required to better understand the role of individual fiber types on the growth of microbes and the overall gut microbial community. This review was registered at PROSPERO as CRD42016053101.

A Potential Problem With The Popularization Of Science

Popularization of science is important, but like a double-edged sword, can have certain drawbacks. Here is an interesting paper, abstract:

Science popularization fulfills the important task of making scientific knowledge understandable and accessible for the lay public. However, the simplification of information required to achieve this accessibility may lead to the risk of audiences relying overly strongly on their own epistemic capabilities when making judgments about scientific claims. Moreover, they may underestimate how the division of cognitive labor makes them dependent on experts. This article reports an empirical study demonstrating that this "easiness effect of science popularization" occurs when laypeople read authentic popularized science depictions. After reading popularized articles addressed to a lay audience, laypeople agreed more with the knowledge claims they contained and were more confident in their claim judgments than after reading articles addressed to expert audiences. Implications for communicating scientific knowledge to the general public are discussed.

I believe that people who do not have a science background tend to underestimate the complexity of science, the high degree of “division of cognitive labor” in science (an expert on one field may know little to nothing about another field), and they also misunderstand the basic idea behind modern science.  On this latter point, science is not really about making final and definitive statements, but rather assigning probabilities to hypothesis based on the available evidence. Therefore, people take a single pronouncement as “the final word” and then get frustrated, or disillusioned with science, when that “final word” is later over-turned by a subsequent “final word.”  Popular writers of science also get facts wring, based in their overestimation of their own understanding of the topic, and pass on these misunderstandings to the public. One hope is that blogs like ApplyForLife will enable people with formal scientific training to directly communicate useful findings directly to the public, with the constant caveat that almost nothing in science is “final” – a point that often eludes the popular writers in scientific topics.

Dioscin And Diabetes

Dioscin can help alleviate negative effects of high glucose in type 2 diabetes through preserving pancreatic cells, mediated by effects on Wnt signaling.  Abstract:

BACKGROUND:

Dysfunction of pancreatic beta cells is related with type 2 diabetes mellitus. Dioscin, a natural steroid saponin, has many pharmacological effects. The aim of this study was to investigate the effects of dioscin on apoptosis of pancreatic beta cells induced by high glucose.

METHODS:

Pancreatic cell line RNAKT-15 was treated with 20 mM glucose with or without different concentrations of dioscin and viability and apoptosis of cells were measured. Western blot assay was used to measure the expression levels of some proteins such as phosphorylated glycogen synthase kinase 3β (GSK-3β) and β-catenin. Enzymelinked immunosorbent assay (ELISA) was used to detect the pro-inflammatory cytokines.

RESULTS:

High-glucose could significantly increase cell RNAKT-15 apoptosis and reduce cell viability (p < 0.01). Dioscin could improve the cell degeneration (p < 0.05). The results demonstrated that high-glucose could increase the proinflammatory cytokines, such as tumor necrosis factor α (TNF-α), interferon-γ (INF-γ), and transforming growth factor-β (TGF-β), while these effects were reduced when treated with dioscin (p < 0.05). Western blot results demonstrated that high-glucose affects p-GSK 3β and β-catenin expression levels (p < 0.01) and dioscin could significantly reduce these two protein levels (p < 0.05).

CONCLUSIONS:

The effects of dioscin against high-glucose induced apoptosis of pancreatic cells may occur through the Wnt signaling pathway. High-glucose led to increased pancreatic cell apoptosis and dioscin could attenuate these impairments. These findings highlight an important role of dioscin in the treatment potential of type 2 diabetes mellitus (T2DM).