Insulin-like growth factors and related proteins in plasma and cerebrospinal fluids of HIV-positive individuals

BACKGROUND: Clinically significant dysregulation of the insulin-like growth factor (IGF) family proteins occurs in HIV-infected individuals, but the details including whether the deficiencies in IGFs contribute to CNS dysfunction are unknown. METHODS: We measured the levels of IGF1, IGF2, IGFBP1, IGFBP2, and IGF2 receptor (IGF2R) in matching plasma and cerebrospinal fluid (CSF) samples of 107 HIV+ individuals from CNS HIV Antiretroviral Therapy Effects Research (CHARTER) and analyzed their associations with demographic and disease characteristics, as well as levels of several soluble inflammatory mediators (TNFα, IL-6, IL-10, IL-17, IP-10, MCP-1, and progranulin). We also determined whether IGF1 or IGF2 deficiency is associated with HIV-associated neurocognitive disorder (HAND) and whether the levels of soluble IGF2R (an IGF scavenging receptor, which we also have found to be a cofactor for HIV infection in vitro) correlate with HIV viral load (VL). RESULTS: There was a positive correlation between the levels of IGF-binding proteins (IGFBPs) and those of inflammatory mediators: between plasma IGFBP1 and IL-17 (β coefficient 0.28, P = 0.009), plasma IGFBP2 and IL-6 (β coefficient 0.209, P = 0.021), CSF IGFBP1 and TNFα (β coefficient 0.394, P < 0.001), and CSF IGFBP2 and TNF-α (β coefficient 0.14, P < 0.001). As IGFBPs limit IGF availability, these results suggest that inflammation is a significant factor that modulates IGF protein expression/availability in the setting of HIV infection. However, there was no significant association between HAND and the reduced levels of plasma IGF1, IGF2, or CSF IGF1, suggesting a limited power of our study. Interestingly, plasma IGF1 was significantly reduced in subjects on non-nucleoside reverse transcriptase inhibitor-based antiretroviral therapy (ART) compared to protease inhibitor-based therapy (174.1 ± 59.8 vs. 202.8 ± 47.3 ng/ml, P = 0.008), suggesting a scenario in which ART regimen-related toxicity can contribute to HAND. Plasma IGF2R levels were positively correlated with plasma VL (β coefficient 0.37, P = 0.021) and inversely correlated with current CD4+ T cell counts (β coefficient −0.04, P = 0.021), supporting our previous findings in vitro. CONCLUSIONS: Together, these results strongly implicate (1) an inverse relationship between inflammation and IGF growth factor availability and the contribution of IGF deficiencies to HAND and (2) the role of IGF2R in HIV infection and as a surrogate biomarker for HIV VL. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12974-015-0288-6) contains supplementary material, which is available to authorized users

Biliary transporter gene mutations in severe intrahepatic cholestasis of pregnancy: Diagnostic and management implications

Background and Aims Clinical syndromes associated with biallelic mutations of bile acid (BA) transporters usually present in childhood. Subtle mutations may underlie intrahepatic cholestasis of pregnancy (ICP) and oral contraceptive steroid (OCS) induced cholestasis. In five women with identified genetic mutations of such transporters, with eight observed pregnancies complicated by ICP, we examined relationships between transporter mutations, clinical phenotypes, and treatment outcomes. Methods Gene mutation analysis for BA transporter deficiencies was performed using Next Generation/Sanger sequencing, with analysis for gene deletions/duplications. Results Intrahepatic cholestasis of pregnancy was early‐onset (9–32 weeks gestation) and severe (peak BA 74–370 μmol/L), with premature delivery (28+1–370 weeks gestation) in 7/8 pregnancies, in utero passage of meconium in 4/8, but overall good perinatal outcomes, with no stillbirths. There was generally no response to ursodeoxycholic acid and variable responses to rifampicin and chelation therapies; naso‐biliary drainage appeared effective in 2/2 episodes persisting post‐partum in each of the two sisters. Episodic jaundice occurring spontaneously or provoked by non‐specific infections, and OCS‐induced cholestasis, had previously occurred in 3/5 women. Two cases showed biallelic heterozygosity for several ABCB11 mutations, one was homozygous for an ABCB4 mutation and a fourth case was heterozygous for another ABCB4 mutation. Conclusions Early‐onset or recurrent ICP, especially with previous spontaneous or OCS‐induced episodes of cholestasis and/or familial cholestasis, may be attributable to transporter mutations, including biallelic mutations of one or more transporters. Response to standard therapies for ICP is often incomplete; BA sequestering therapy or naso‐biliary drainage may be effective. Optimized management can produce good outcomes despite premature birth and evidence of fetal compromise

Biliary transporter gene mutations in severe intrahepatic cholestasis of pregnancy: Diagnostic and management implications

Background and Aims Clinical syndromes associated with biallelic mutations of bile acid (BA) transporters usually present in childhood. Subtle mutations may underlie intrahepatic cholestasis of pregnancy (ICP) and oral contraceptive steroid (OCS) induced cholestasis. In five women with identified genetic mutations of such transporters, with eight observed pregnancies complicated by ICP, we examined relationships between transporter mutations, clinical phenotypes, and treatment outcomes. Methods Gene mutation analysis for BA transporter deficiencies was performed using Next Generation/Sanger sequencing, with analysis for gene deletions/duplications. Results Intrahepatic cholestasis of pregnancy was early‐onset (9–32 weeks gestation) and severe (peak BA 74–370 μmol/L), with premature delivery (28+1–370 weeks gestation) in 7/8 pregnancies, in utero passage of meconium in 4/8, but overall good perinatal outcomes, with no stillbirths. There was generally no response to ursodeoxycholic acid and variable responses to rifampicin and chelation therapies; naso‐biliary drainage appeared effective in 2/2 episodes persisting post‐partum in each of the two sisters. Episodic jaundice occurring spontaneously or provoked by non‐specific infections, and OCS‐induced cholestasis, had previously occurred in 3/5 women. Two cases showed biallelic heterozygosity for several ABCB11 mutations, one was homozygous for an ABCB4 mutation and a fourth case was heterozygous for another ABCB4 mutation. Conclusions Early‐onset or recurrent ICP, especially with previous spontaneous or OCS‐induced episodes of cholestasis and/or familial cholestasis, may be attributable to transporter mutations, including biallelic mutations of one or more transporters. Response to standard therapies for ICP is often incomplete; BA sequestering therapy or naso‐biliary drainage may be effective. Optimized management can produce good outcomes despite premature birth and evidence of fetal compromise.</p

Unleashing the contribution of nanoparticles in reforming Low-Carbon Solutions: Current Status, Trend, and prospects

The alarming climate change that has occurred on Earth has increased the urgency of reducing global CO2 emissions. In response to this longstanding issue, many countries and organizations have been actively strengthening the implementation of low-carbon strategies as a crucial step toward achieving the larger goal of net-zero carbon emissions by 2050. Nanoparticles, extremely tiny particles with at least one of their dimensions ranging from 1 nm to 100 nm, played a significant role in advancing diverse low-carbon technologies. While it was not emphasized previously, the present article serves as the first note to look into the utilization of this unique matter, specifically in (i) carbon capture and storage (CCS) technology, (ii) catalytic conversion and upcycle of CO2 into value-added fuels and chemicals, (iii) the development of low-carbon and carbon–neutral fuels with improved combustion properties, (iv) the enhancement of low-carbon energy harvesting technology, (v) the development of lithium-ion batteries for low-carbon mobility, and their applications in (vi) improved crude oil extraction technology. Nanoparticles have gained favour in low-carbon technologies primarily because of their significantly larger specific surface area, which leads to better interfacial interaction, reactivity, adsorption capacity, sensitivity, and other properties. Here, the status and progress in the aforementioned nanoparticle-enabled low-carbon technologies are discussed and reviewed. Considering that it is essential to attain carbon neutrality in the long run, the future outlook in this study area is proposed to be focused on the pursuit of manufacturing/synthesis of nanoparticles in an environmentally friendly, reduced carbon footprint manner. It is envisaged that this study will offer a holistic view as well as new insights into the role of nanoparticles in paving the way towards a low-carbon future

On the Rapid Synthesis of Reduced Graphene Oxide via Ultrasound-Promoted Eco-Friendly Reduction Approach and Its Effects on Physicochemical Properties

The common synthesis approach of reduced graphene oxide (rGO) using toxic reducing agents poses a threat to environmental pollution. This study used banana peel extract as a green reducing agent for the synthesis of rGO. Ultrasonication was assimilated to expedite the synthesis process. For comparison, rGO was also produced by reducing GO with hydrazine treatment under conventional stirring. Both morphological (SEM) and physicochemical (FTIR and XRD) studies have revealed that banana peel extract can reduce GO to rGO, although its reducing effect is much weaker compared to hydrazine. Despite this, the rGO produced using banana peel extract with the assimilation of ultrasonication technique has a greater interlayer spacing than that formed under the conventional stirring method. In terms of electrical properties, the electrical conductance of hydrazine-produced rGO (5.69×10−6 S) is higher than the banana peel extract-produced rGO (3.55×10−6 S–4.56×10−6 S). Interestingly, it was found that most of the rGO produced by banana peel extract under ultrasound assistance has higher or comparable electrical conductance compared to the rGO produced by banana peel extract under stirring method. This implies the feasibility of using short-period ultrasound to replace conventional stirring in rGO synthesis

Borophene Oxide and Graphene Oxide for Renewable Energy: A Comparative Study on their Catalytic Performance in Sodium Borohydride Hydrolysis for Hydrogen Generation

The recent rise of borophene as a new 2D material has triggered competition with the well-known graphene. The present work serves as the first attempt to compare the efficiency of borophene oxide (BO) and graphene oxide (GO) in catalyzing NaBH 4 hydrolysis for hydrogen generation. For a fair comparison, the BO and GO particles are synthesized using the same improved Hummers’ method. Morphological studies show that both BO and GO appear in plate-like shapes; however, GO exhibits a more scrunched and rippled structure with larger interlayer spacing. BO and GO exhibit more oxygen-containing groups than their bulk counterparts. X-ray diffraction analysis indicates that BO has a reduced crystallinity, while GO exhibits turbostratic disorder. Regarding catalytic properties, both BO and GO are found to be on par as catalysts, increasing hydrogen yield from NaBH hydrolysis by 25 times in 30 s, offering new insights for the clean energy industry