Nuclear factor (NF)-κB plays an important role in the innate immune response by inducing antiviral genes\' expression. However, the herpes simplex virus 1 (HSV-1) virus has developed multiple ways to interfere with NF-κB activity to escape the host antiviral response. Here, we found that HSV-1 envelope glycoprotein L(gL) markedly inhibits interferon (IFN) production and its downstream antiviral genes. Our results showed that ectopic expression of gL inhibited IFN-β promoter activation, and decreased IFN-β production, the expression of IFN-stimulated genes (ISGs), and inhibited immunologic stimulant (poly I:C) induced activation of IFN signaling pathway. Depletion of gL by short interfering RNA (siRNA) significantly upregulated IFN-β and ISG production. Further study showed that the N-terminus of the gL bound to the Rel homology domain (RHD) of the p65 and concealed the nuclear localization signal of p65, thereby impeding the translocation of phosphorylated p65 to the nucleus. In summary, our findings indicated that the N-terminal of HSV-1 gL contributes to immune invasion by inhibiting the nuclear translocation of p65.

The glycemic index (GI) and glycemic load (GL) of a single food item has been used to monitor blood glucose level. However, concerns regarding the clinical relevance of the GI or GL have been raised on their applicability to a combination of several foods consumed as meal. This study aimed to investigate the glycemic response after consuming commercially purchased ready-to-eat meal and to develop the GL prediction formula using the composition of nutrients in each meal. Glycemic responses were measured in healthy adults with various mixed meals comprising approximately 25 g, 50 g, and 75 g of carbohydrates. After fasting, participants consumed test meals, and the glycemic response was measured for a subsequent 120 min. The GI and GL values for mixed meals were calculated as area under curve for each participant. For the prediction formula, 70 mixed meals were analyzed, of which the GI and GL values of 64 participants were used. The prediction formula produced was as follows: GL = 19.27 + (0.39 × available carbohydrate) - (0.21 × fat) - (0.01 × protein2) - (0.01 × fiber2). We hope that this prediction formula can be used as a useful tool to estimate the GL after consuming ready-to-eat meals.

UNASSIGNED: The Marek\'s disease virus (MDV) is a neoplastic disease causing serious economic losses in poultry production. This study aimed to investigate MDV occurrence in poultry flocks in the Lower Egypt during the 2020 breakout and genetically characterized Meq, gL, and ICP4 genes in field strains of MDV.
UNASSIGNED: Forty samples were collected from different breeds from eight Egyptian governorates in 2020. All flocks had received a bivalent vaccine (herpesvirus of turkey FC-126 + Rispens CVI988). However, weight loss, emaciation, reduced egg production, paralysis, and rough/raised feather follicles occurred. Samples were collected from feather follicles, liver, spleen, and nerve tissue for diagnosis by polymerase chain reaction. MDV genetic characterization was then performed by sequencing the Meq, gL, and ICP4 genes of five positive samples representing different governorates and breeds.
UNASSIGNED: A total of 28 samples were positive for MDV field strains, while two were related to MDV vaccinal strains. All samples tested negative for ALV (A, B, C, D, and J) and REV. Phylogenetic analysis of the Meq gene of sequenced samples revealed that all MDVs were related to the highly virulent European viruses (Gallid herpesvirus 2 ATE and PC12/30) with high amino acid (A.A.) identity 99.2-100%. Alternatively, there was low A.A. identity with the vaccine strains CVI988 and 3004 (up to 82.5%). These results indicate that further investigation of the efficacy of current Egyptian vaccines is required. The Egyptian strains also harbor a specific mutation, allowing clustering into two subgroups (A and B). By mutation analysis of the Meq gene, the Egyptian viruses in our study had R101K, P217A, and E263D mutations present in all Egyptian viruses. Furthermore, R176A and T180A mutations specific to our strains contributed to the high virulence of highly virulent strains. There were no mutations of the gL or ICP4 genes.
UNASSIGNED: Further studies should evaluate the protection contributed by current vaccines used in Egypt.

Species-specific guinea pig cytomegalovirus (GPCMV) causes congenital CMV and the virus encodes homolog glycoprotein complexes to human CMV, including gH-based trimer (gH/gL/gO) and pentamer-complex (PC). Platelet-derived growth factor receptor alpha (gpPDGFRA), only present on fibroblast cells, was identified via CRISPR as the putative receptor for PC-independent GPCMV infection. Immunoprecipitation assays demonstrated direct interaction of gH/gL/gO with gpPDGFRA but not in absence of gO. Expression of viral gB also resulted in precipitation of gB/gH/gL/gO/gpPDGFRA complex. Cell-cell fusion assays determined that expression of gpPDGFRA and gH/gL/gO in adjacent cells enabled cell fusion, which was not enhanced by gB. N-linked gpPDGFRA glycosylation inhibition had limited effect and blocking tyrosine kinase (TK) transduction had no impact on infection. Ectopically expressed gpPDGFRA or TK-domain mutant in trophoblast or epithelial cells previously non-susceptible to GPCMV(PC-) enabled viral infection. In contrast, transient human PDGFRA expression did not complement GPCMV(PC-) infection, a potential basis for viral species specificity.

The increasing prevalence of type 2 diabetes (T2D) worldwide calls for effective approaches to its management. Strategies for diabetes have generally focused on optimizing overall glycemic control as assessed by glycated hemoglobin (HbA1c) and fasting plasma glucose (FPG) values. However, since 2001, the American Diabetes Association has established postprandial glucose (PPG) as an independent contributor to both HbA1c and diabetes complications, and increasing evidence suggests that all three glycemic parameters of HbA1c, FPG, and postprandial glucose (PPG) are independently important.
OBJECTIVE: The objective of this review was to comprehensively summarize the literature on the effects of nutritional strategies incorporating glycemic index (GI)/glycemic load (GL) on the postprandial hyperglycemia in people with T2D, as well as to provide recommendations for effective dietary strategies addressing both the dietary glycemic index and load in clinical practice.
METHODS: An advanced Pubmed search was conducted. A total of 10 randomized controlled studies met the inclusion criteria. Six studies compared low-GI with higher GI meals, three included studies that compared reduced carbohydrate content with higher carbohydrate content, and one study compared meals of low-GI (with high or low fiber) with meals of higher GI (with high or low fiber).
RESULTS: Most of the clinical trials resulted in significant improvement (p < 0.05) of postprandial hyperglycemia. Conclusions: Either reducing the amount of carbohydrate in a meal or increasing consumption of soluble fiber has a favorable effect on postprandial glucose excursions.

OBJECTIVE: To identify the association between the dietary carbohydrate indexes, such as dietary glycemic index (DGI) and load (DGL), dietary insulin index (DII) and load (DIL), with the possibility of cataract.
METHODS: This case-control study consisted of 101 new cases of cataract and 202 controls. DGI and DGL were computed through DGI values previously published. DII was also calculated based on dietary insulin index data published previously.
RESULTS: There was a significant positive association between the highest quartiles of DGI (OR = 6.56; 95% CI = 2.67-16.06; P < 0.001), DGL (OR = 6.17; 95% CI = 1.93-19.37; P = 0.002) and DIL (OR = 4.17; 95% CI = 1.41-12.27; P = 0.004) with risk of cataract, compared to those on the lowest quartile, but not for DII (OR = 0.85; 95% CI = 0.39-1.86; P = 0.82). Furthermore, after stratifying groups by BMI, a significant direct association between highest quartile of DGI (OR = 6.76; 95% CI = 2.49-18.38; P < 0.001) and DGL (OR = 3.45; 95% CI = 0.96-12.37; P = 0.05) with risk of cataract was evident in individuals with elevated BMI (BMI≥25).
CONCLUSIONS: We found a significant, direct, relationship between DGI, DGL and DIL with risk of cataract. However, the association between DII and the risk of cataract was not significant, even after adjusting for related confounders.

Kaposi\'s sarcoma-associated herpesvirus (KSHV) is the etiological agent of Kaposi\'s sarcoma (KS), one of the most prevalent cancers of people living with HIV/AIDS in sub-Saharan Africa. The seroprevalence for KSHV is high in the region, and no prophylactic vaccine against the virus is available. In this study, we characterized the antigenic targets of KSHV-specific neutralizing antibodies (nAbs) in asymptomatic KSHV-infected individuals and KS patients with high nAbs titers. We quantified the extent to which various KSHV envelope glycoproteins (gB, ORF28, ORF68, gH, gL, gM, gN and gpK8.1) adsorbed/removed KSHV-specific nAbs from the plasma of infected individuals. Our study revealed that plasma from a majority of KSHV neutralizers recognizes multiple viral glycoproteins. Moreover, the breadth of nAbs responses against these viral glycoproteins varies among endemic KS, epidemic KS and asymptomatic KSHV-infected individuals. Importantly, among the KSHV glycoproteins, the gH/gL complex, but neither gH nor gL alone, showed the highest adsorption of KSHV-specific nAbs. This activity was detected in 80% of the KSHV-infected individuals regardless of their KS status. The findings suggest that the gH/gL complex is the predominant antigenic determinant of KSHV-specific nAbs. Therefore, gH/gL is a potential target for development of KSHV prophylactic vaccines.

Historically, analysis of intragastric exfoliative cytology (IEC) of gastric cancer (GC) was used with a diagnostic intent only. With the successful advent of endoscopic biopsy, the rate of detection of GC has improved worldwide and, as a consequence, IEC has been progressively abandoned. Today, however, there is a renewed interest in this field of research, as witnessed by several pertinent publications. As discussed in this review, in fact, currently the importance of analyzing IEC in patients with early and advanced GC seems to reside in its clinicopathological and prognostic significance. In fact, compared to non-sloughing tumors, GC exhibiting intragastric exfoliation was recently associated with an aggressive tumor phenotype (characterized by deeper infiltration of the gastric wall, lymph nodal or distant metastases, angiolymphatic and perineural invasion) and poorer prognosis. Adoption of IEC examination in routine practice might help identify patients at higher risk of developing local recurrence and peritoneal metastasis from early and advanced GC, optimizing their treatment and improving quality of life and life expectancy.

Glycyrrhetinic acid 3-O-mono-β-d-glucuronide (GAMG), which possesses a higher sweetness and stronger pharmacological activity than those of glycyrrhizin (GL), can be obtained by removal of the distal glucuronic acid (GlcA) from GL. In this study, we isolated a β-glucuronidase (TpGUS79A) from the filamentous fungus Talaromyces pinophilus Li-93 that can specifically and precisely convert GL to GAMG without the formation of the by-product glycyrrhetinic acid (GA) from the further hydrolysis of GAMG. First, TpGUS79A was purified and identified through matrix-assisted laser desorption ionization-tandem time of flight mass spectrometry (MALDI-TOF-TOF MS) and deglycosylation, indicating that TpGUS79A is a highly N-glycosylated monomeric protein with a molecular mass of around 85 kDa, including around 25 kDa of glycan moiety. The gene for TpGUS79A was then cloned and verified by heterologous expression in Pichia pastoris TpGUS79A belonged to glycoside hydrolase family 79 (GH79) but shared low amino acid sequence identity (<35%) with the available GH79 GUS enzymes. TpGUS79A had strict specificity toward the glycan moiety but poor specificity toward the aglycone moiety. Interestingly, TpGUS79A recognized and hydrolyzed the distal glucuronic bond of GL but could not cleave the glucuronic bond in GAMG. TpGUS79A showed a much higher catalytic efficiency on GL (kcat/Km of 11.14 mM-1 s-1) than on the artificial substrate pNP β-glucopyranosiduronic acid (kcat/Km of 0.01 mM-1 s-1), which is different from the case for most GUSs. Homology modeling, substrate docking, and sequence alignment were employed to identify the key residues for substrate recognition. Finally, a fed-batch fermentation in a 150-liter fermentor was established to prepare GAMG through GL hydrolysis by T. pinophilus Li-93. Therefore, TpGUS79A is potentially a powerful biocatalyst for environmentally friendly and cost-effective production of GAMG.IMPORTANCE Compared to chemical methods, the biotransformation of glycyrrhizin (GL) into glycyrrhetinic acid 3-O-mono-β-d-glucuronide (GAMG), which has a higher sweetness and stronger pharmacological activity than those of GL, via catalysis by β-glucuronidase is an environmentally friendly approach due to the mild reaction conditions and the high yield of GAMG. However, currently available GUSs show low substrate specificity toward GL and further hydrolyze GAMG to glycyrrhetinic acid (GA) as a by-product, increasing the difficulty of subsequent separation and purification. In the present study, we succeeded in isolating a novel β-glucuronidase (named TpGUS79A) from Talaromyces pinophilus Li-93 that specifically hydrolyzes GL to GAMG without the formation of GA. TpGUS79A also shows higher activity on GL than those of the previously characterized GUSs. Moreover, the gene for TpGUS79A was cloned and its function verified by heterologous expression in P. pastoris Therefore, TpGUS79A can serve as a powerful biocatalyst for the cost-effective production of GAMG through GL transformation.

Herpes simplex virus (HSV) is an important human pathogen. It enters cells through an orchestrated process that requires four essential glycoproteins, gD, gH/gL, and gB, activated in cascade fashion by receptor-binding and signaling. gH/gL heterodimer is conserved across the Herpesviridae family. HSV entry is enabled by gH/gL interaction with αvβ6- or αvβ8-integrin receptors. We report that the interaction of virion gH/gL with integrins resulted in gL dissociation and its release in the medium. gL dissociation occurred if all components of the entry apparatus-receptor-bound gD and gB-were present and was prevented if entry was blocked by a neutralizing monoclonal antibody to gH or by a mutation in gH. We propose that (i) gL dissociation from gH/gL is part of the activation of HSV glycoproteins, critical for HSV entry; and (ii) gL is a functional inhibitor of gH and maintains gH in an inhibited form until receptor-bound gD and integrins signal to gH/gL.