Background: To find the relationship between toll-like receptor (TLR) gene variants and human immunodeficiency virus (HIV) infection and clinical findings, which could inform clinical decisions and vaccination strategies. Method: Four databases were searched for articles that were published on or before Jul.1, 2020. Review Manager 5.3 software was applied to perform meta-analysis to explore. Results: A total of 10 studies involving 20 genes, 3697 cases, and 6498 controls were included in this systematic review. TLR2 –196 to –174 Ins/Del (odds ratio [OR] = 1.562; P = .002), TLR4 rs4986790 (OR = 2.05; P = .002), TLR3 rs3775291 (OR = 0.25; P = .03), TLR7 rs179008 ( P = .002), TLR7 rs2074109 (OR = 0.27, P = .019) were found associated with HIV infection. TLR2 –196 to –174, TLR4 rs4986790, TLR7 rs179008, TLR8 rs3764880, TLR9 rs352140 were found associated with clinical findings of HIV infection. We identified 5 case-control studies in meta-analysis, involving 695 cases and 729 controls on TLR7 rs179008 polymorphism, totaling 652 cases and 614 controls on TLR9 rs352140 polymorphism. In meta-analysis, we employed various genetic models. The T allele of TLR7 rs179008 was conferred the risk of HIV infection (T vs A: OR = 1.25, P A = .02). An increased risk of HIV infection was found for individuals with the TLR9 rs352140 GG genotype (GG vs AA: OR = 1.50, P A = .04). Conclusions: The systematic review indicated that TLR7 rs179008 T allele provides risk effects for HIV infection. TLR9 rs352140 GG genotype may associate with HIV infection.
Here we establish that, contrary to expectations, Caenorhabditis elegans nematode worms possess a color discrimination system despite lacking any opsin or other known visible light photoreceptor genes. We found that white light guides C. elegans foraging decisions away from harmful bacteria that secrete a blue pigment toxin. Absorption of amber light by this blue pigment toxin alters the color of light sensed by the worm, and thereby triggers an increase in avoidance. By combining narrow-band blue and amber light sources, we demonstrated that detection of the specific blue:amber ratio by the worm guides its foraging decision. These behavioral and psychophysical studies thus establish the existence of a color detection system that is distinct from those of other animals.3 Main text:C. elegans live in decomposing organic matter where they feed on microorganisms 1-3 , some of which secrete colorful pigments. While C. elegans lack any specialized photoreceptor cells or opsin genes, they possess an illuminance sensing system that mediates rapid escape responses to short-wavelength light 4-6 . However, it is unknown whether C. elegans use light information, potentially including color, to inform complex decisions like foraging in environments containing colorful food sources. To address this question, we first tested whether white light alters foraging decisions on P. aeruginosa bacterial lawns containing the blue pigment toxin pyocyanin, one of a number of small molecule phenazine toxins secreted by P. aeruginosa 7-10 . We employed an 8 kilolux LED array white light source to mimic naturalistic lighting levels (Fig. 1a, Supplementary Fig. 1a). Previous studies have shown that foraging decisions to remain on or leave a bacterial lawn are guided by a variety of factors 11,12 . Worms remain on bacterial lawns that are easy to eat and support growth, while leaving lawns that are of poor nutritive quality, repulsive, or pathogenic [11][12][13][14][15][16] . Worms are initially attracted to P. aeruginosa lawns, but over a time course of hours, as the P. aeruginosa continues to divide and secrete toxins, they respond to its increasingly aversive qualities and begin to leave 14,15,[17][18][19][20] .Whether light plays a role in guiding avoidance of P. aeruginosa has never been tested. Here we employed a standard lawn avoidance assay, placing worms on a P. aeruginosa lawn in the center of an agar plate, and quantified the time course of avoidance as the fraction of worms found off the lawn (Fig. 1a). Consistent with prior studies, worms gradually avoid P. aeruginosa strain PA14 over a span of many hours 14,15,[17][18][19][20] (Fig. 1a). Surprisingly, however, this avoidance is dramatically potentiated by white light (Fig. 1b). White light does not potentiate avoidance of
Arterial hypertension is considered the most prevalent risk factor for stroke. Both pathophysiologic and clinical data previously acquired suggest a strong correlation between the hemodynamic nature of arterial hypertension and an increase in the risk of ischemic insult to tissues. However, the knowledge of specific molecular interactions between hypertension and ischemic stroke (IS) is limited. In this study, we performed systematic bioinformatics analysis of stroke-prone spontaneous hypertensive brain tissue samples of rats (GSE41452), middle cerebral artery occlusion of brain tissue samples of rats (GSE97537), and peripheral blood array data of IS patients (GSE22255). We identified that Fos, an immediate-early gene (IEG) that responds to alterations in arterial blood pressure, has a strong correlation with the occurrence and prognosis of IS. To further evaluate the potential function of Fos, the oxygen–glucose deprivation model and RNA sequencing of HT22 neuronal cells were performed. Consistent with the sequencing results, real-time quantitative PCR and Western blot indicate that Fos was elevated at 3 h and returned to normal levels at 6 h after oxygen–glucose deprivation. Knock-down of Fos by lentivirus significantly increased the oxidative stress level, neuronal apoptosis, and inhibited the mitochondrial function. In conclusion, Fos acts as an important link between hypertension and IS. Furthermore, Fos can be used as a potential biomarker for target therapy in the prevention of stroke among hypertensive patients and also potential treatment targeting apoptosis and oxidative stress after its onset.
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