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Huntington's Disease as progressive neurological disorders associated with motor, behavioral, and cognitive impairment poses a therapeutic challenge in case of limited responsiveness to established therapeutics. Pallidal deep brain stimulation and neurorestorative strategies (brain grafts) scoping to modulate fronto-striatal circuits have gained increased recognition for the treatment of refractory Huntington's disease (HD). A review (2000–2022) was performed in PubMed, Embase, and Cochrane Library covering clinical trials conceptualized to determine the efficacy and safety of invasive, stereotactic-guided deep-brain stimulation and intracranial brain-graft injection targeting the globus pallidus and adjunct structures (striatum). Stereotactic brain-grafting strategies were performed in few HD patients with inconsistent findings and mild-to-moderate clinical responsiveness with a recently published large, randomized-controlled trial (NCT 00190450) yielding negative results. We identified 19 in-human DBS trials (uncontrolled) targeting the globus pallidus internus/externus along with randomized-controlled trial pending report (NCT 02535884). We did not detect any significant changes in the UHDRS total score after restorative injections, while in contrast, the use of deep-brain stimulation resulted in a significant reduction of chorea. GPi-DBS should be considered in cases where selective chorea is present. However, both invasive therapies remain experimental and are not ready for the implementation in clinical use. [ABSTRACT FROM AUTHOR]

As TNFAIP8 plays an important role in the development of cancer, several studies have analyzed the relationship between potential functional polymorphic loci of the TNFAIP8 gene and cancer risk. However, some results were inconsistent. Therefore, the current study aims to systematically assess the relationship between these genetic polymorphisms and cancer risk using a meta-analysis approach. Relevant studies were obtained from CNKI, Embase, Web of Science, and PubMed databases. RevMan software was used to conduct data analysis. The combined analysis containing four studies with 2786 cancer patients and 2550 control individuals indicated that rs11064 polymorphism was not associated with cancer risk. The pooled analysis containing three studies with 950 cancer patients and 1036 control individuals showed that rs1045241 polymorphism was associated with cancer risk in the heterozygous model (CT vs. CC: OR = 1.34, 95%CI = 1.10‐1.62, Pz=0.003) and dominant model [(TT + CT) vs. CC: OR = 1.38, 95% CI = 1.15-1.66, Pz=0.0006], but not in other models. The pooled analysis containing two studies 436 cancer patients and 479 control individuals showed that rs1045242 polymorphism was associated with cancer risk in the heterozygous model (AG vs. AA: OR = 1.52, 95%CI = 1.14-2.03, Pz=0.005), dominant model [(GG + AG) vs. AA: OR = 1.56, 95% CI = 1.18-2.07, Pz=0.002] and allelic model (G vs. A: OR = 1.48, 95%CI = 1.16-1.90, Pz=0.002). In conclusion, the current findings suggest that the rs1045241 and rs1045242 polymorphisms located on the TNFAIP8 gene were associated with cancer risk in Chinese population, and may serve as valuable genetic susceptibility markers. [ABSTRACT FROM AUTHOR]

In recent years, several case-control studies have explored the association between the rs7763881 locus polymorphism of the HULC gene and cancer risk, however, the findings have been inconsistent. Therefore, a meta-analysis was conducted to clarify the association. Relevant case-control studies were obtained from CNKI, Embase, Web of Science and PubMed databases. RevMan software was used to perform data analysis. A total of 8 case-control studies containing 4036 cases and 5286 controls were included in the current meta-analysis. The overall analysis results showed no significant association between the rs7763881 locus polymorphism and cancer risk. However, stratified analysis based on cancer type showed that the rs7763881 locus polymorphism was associated with the decreased risk of hepatocellular cancer, colorectal cancer and esophageal cancer. In conclusion, the current findings suggest that the rs7763881 polymorphic loci located on the HULC gene may serve as a biomarker for determining an individual's risk of hepatocellular cancer, colorectal cancer and esophageal cancer. [ABSTRACT FROM AUTHOR]

Regulators of G protein signaling (RGSs) are proteins that negatively regulate G protein signal transduction. In this study, seven putative RGSs were characterized in the nematode-trapping (NT) fungus, Arthrobotrys oligospora. Deleting Rgs genes significantly increased intracellular cAMP levels, and caused defects in mycelia growth, stress resistance, conidiation, trap formation, and nematocidal activity. In particular, the ΔAoFlbA mutant was unable to produce conidia and traps. Transcriptomic analysis showed that amino acid metabolic and biosynthetic processes were significantly enriched in the ΔAoFlbA mutant compared to WT. Interestingly, Gas1 family genes are significantly expanded in A. oligospora and other NT fungi that produce adhesive traps, and are differentially expressed during trap formation in A. oligospora. Disruption of two Gas1 genes resulted in defective conidiation, trap formation, and pathogenicity. Our results indicate that RGSs play pleiotropic roles in regulating A. oligospora mycelial growth, development, and pathogenicity. Further, AoFlbA is a prominent member and required for conidiation and trap formation, possibly by regulating amino acid metabolism and biosynthesis. Our results provide a basis for elucidating the signaling mechanism of vegetative growth, lifestyle transition, and pathogenicity in NT fungi. [ABSTRACT FROM AUTHOR]