To meet the high consumer demand, butter production has increased over the last few years. As a result, the buttermilk (BM) co-produced volumes require new ways of adding value, such as in cheese manufacturing. However, BM use in cheese milk negatively influences the cheesemaking process (e.g., altered coagulation properties) and the product\'s final quality (e.g., high moisture content). The concentration of BM by ultrafiltration (UF) could potentially facilitate its use in cheese manufacturing through an increased protein content while maintaining the milk salt balance. Simultaneously, little is known about the digestion of UF BM cheese. Therefore, this study aimed to characterize the impact of UF BM on cheese manufacture, its structure, and its behavior during in vitro digestion. A 2-fold UF concentrated BM was used for cheese manufacture (skim milk [SM] - control). Compositional, textural, and microstructural analyses of cheeses were first conducted. In a second step, the cheeses were fed into an in vitro TNO gastrointestinal digestion model (TIM-1) of the stomach and small intestine and protein and phospholipid (PL) bioaccessibility was studied. The results showed that UF BM cheese significantly differed from SM cheese regarding its composition, hardness (p < 0.05) and microstructure. However, in TIM-1, UF BM and SM cheeses showed similar digestion behavior as a percentage of protein and PL intake. Despite relatively more non-digested and non-absorbed PL in the ileum efflux of UF BM cheese, the initially higher PL concentration contributes to an enhanced nutritional value compared to SM cheese. To our knowledge, this study is the first to compare the bioaccessibility of proteins and PL from UF BM and SM cheeses.

The kidney injury molecule (KIM)-1 is shed from proximal tubular cells in acute kidney injury (AKI), relaying tubular epithelial proliferation. Additionally, KIM-1 portends complex immunoregulation and is elevated after exposure to lipopolysaccharides. It thus may represent a biomarker in critical illness, sepsis, and sepsis-associated AKI (SA-AKI). To characterise and compare KIM-1 in these settings, we analysed KIM-1 serum concentrations in 192 critically ill patients admitted to the intensive care unit. Irrespective of kidney dysfunction, KIM-1 serum levels were significantly higher in patients with sepsis compared with other critical illnesses (191.6 vs. 132.2 pg/mL, p = 0.019) and were highest in patients with urogenital sepsis, followed by liver failure. Furthermore, KIM-1 levels were significantly elevated in critically ill patients who developed AKI within 48 h (273.3 vs. 125.8 pg/mL, p = 0.026) or later received renal replacement therapy (RRT) (299.7 vs. 146.3 pg/mL, p < 0.001). KIM-1 correlated with markers of renal function, inflammatory parameters, hematopoietic function, and cholangiocellular injury. Among subcomponents of the SOFA score, KIM-1 was elevated in patients with hyperbilirubinaemia (>2 mg/dL, p < 0.001) and thrombocytopenia (<150/nL, p = 0.018). In univariate and multivariate regression analyses, KIM-1 predicted sepsis, the need for RRT, and multi-organ dysfunction (MOD, SOFA > 12 and APACHE II ≥ 20) on the day of admission, adjusting for relevant comorbidities, bilirubin, and platelet count. Additionally, KIM-1 in multivariate regression was able to predict sepsis in patients without prior (CKD) or present (AKI) kidney injury. Our study suggests that next to its established role as a biomarker in kidney dysfunction, KIM-1 is associated with sepsis, biliary injury, and critical illness severity. It thus may offer aid for risk stratification in these patients.

T-cell immunoglobulin and mucin structural domain 1 (TIM-1, also known as hepatitis A virus cell receptor 1) is a co-stimulatory molecule that is expressed predominantly on the surface of T cells. TIM-1 promotes the activation and proliferation of T cells, cytokine secretion, and can also be overexpressed in various types of cancer. Upregulation of TIM-1 expression may be associated with the development and progression of cancer. After reviewing the literature, we propose that TIM-1 affects tumour development mainly through two pathways. In the Direct pathway: overexpression in tumours activates tumour-related signaling pathways, mediates the proliferation, apoptosis, invasion and metastasis, and directly affects tumour development directly. In the indirect pathway: In addition to changing the tumour microenvironment and influencing the growth of tumours, TIM-1 binds to ligands to encourage the activation, proliferation, and generation of cytokines by immune cells. This review examines how TIM-1 stimulates the development of tumours in direct and indirect ways, and how TIM-1 is exploited as a target for cancer therapy.

Hantaan virus (HTNV) is a major public health concern due to its ability to cause hemorrhagic fever with renal syndrome (HFRS) in Eurasia. Symptoms of HFRS include fever, hemorrhage, immune dysfunction and renal impairment, and severe cases can be fatal. T cell-mediated adaptive immune responses play a pivotal role in countering HTNV infection. However, our understanding of HTNV and T cell interactions in the disease progression is limited. In this study, we found that human CD4+ T cells can be directly infected with HTNV, thereby facilitating viral replication and production. Additionally, T-cell immunoglobulin and mucin 1 (TIM-1) participated in the process of HTNV infection of Jurkat T cells, and further observed that HTNV enters Jurkat T cells via the clathrin-dependent endocytosis pathway. These findings not only affirm the susceptibility of human CD4+ T lymphocytes to HTNV but also shed light on the viral tropism. Our research elucidates a mode of the interaction between the virus infection process and the immune system. Critically, this study provides new insights into the pathogenesis of HTNV and the implications for antiviral research.

Microencapsulation of probiotics is a main technique employed to improve cell survival in gastrointestinal tract (GIT). The present study investigated the impact of utilizing proteins i.e. Whey Protein Isolates (WPI), Pea Protein Isolates (PPI) or (WPI + PPI) complex based microbeads as encapsulating agents on the encapsulation efficiency (EE), diameter, morphology along with the survival and viability of Bifidobacterium infantis ATCC 15697. Results revealed that WPI + PPI combination had the highest EE% of the probiotics up to 94.09 % and the smoothest surface with less visible holes. WPI based beads revealed lower EE% and smaller size than PPI based ones. In addition, WPI based beads showed rough surface with visible signs of cracks, while PPI beads showed dense surfaces with pores and depressions. In contrast, the combination of the two proteins resulted in compact and smooth beads with less visible pores/wrinkles. The survival in gastrointestinal tract (GIT) was observed through TNO in-vitro gastrointestinal model (TIM-1) and results illustrated that all microbeads shrank in gastric phase while swelled in intestinal phase. In addition, in-vitro survival rate of free cells was very low in gastric phase (18.2 %) and intestinal phase (27.5 %). The free cells lost their viability after 28 days of storage (2.66 CFU/mL) with a maximum log reduction of 6.76, while all the encapsulated probiotic showed more than 106-7 log CFU/g viable cell. It was concluded that encapsulation improved the viability of probiotics in GIT and utilization of WPI + PPI in combination provided better protection to probiotics.

The differences in wheat flour characteristics caused by ancient (pestle and mortar), old (stone hand mill), and modern (roller and cyclone) milling techniques and their effect on in vitro starch digestibility of wheat porridge using the simulated TIM Gastrointestinal Model (TIM-1) were investigated. Ancient flour (AF) was the coarsest flour (∼70 % is >1000 µm), followed by old wholemeal flour (OWF) and old refined flour (ORF) with similar particle size distribution showing one prominent peak (at ∼1000 µm for OWF and ∼800 µm for ORF). Modern refined flour (MRF) had a monomodal distribution centered at a particle size of ∼100 μm, while modern wholemeal flour (MWF) particle size was distributed between 40 and 600 μm. MRF and MWF porridges had higher cumulative sugar bioaccessibility than OWF and AF porridges, with ORF porridge having an intermediate cumulative sugar bioaccessibility. Characterizing the cumulative sugar bioaccessibility profile with a shifted logistic model allows identifying that the maximum sugar bioaccessibility and rate of sugar release were significantly higher (p < 0.05) for MRF and MWF compared to OWF and AF porridges, while the induction times were shorter, demonstrating the importance of processing on modulating starch digestibility.

Ebola virus (EBOV) and Bundibugyo virus (BDBV) belong to the family Filoviridae and cause a severe disease in humans. We previously isolated a large panel of monoclonal antibodies from B cells of human survivors from the 2007 Uganda BDBV outbreak, 16 survivors from the 2014 EBOV outbreak in the Democratic Republic of the Congo, and one survivor from the West African 2013-2016 EBOV epidemic. Here, we demonstrate that EBOV and BDBV are capable of spreading to neighboring cells through intercellular connections in a process that depends upon actin and T cell immunoglobulin and mucin 1 protein. We quantify spread through intercellular connections by immunofluorescence microscopy and flow cytometry. One of the antibodies, BDBV223, specific to the membrane-proximal external region, induces virus accumulation at the plasma membrane. The inhibiting activity of BDBV223 depends on BST2/tetherin.

The maple syrup industry generates substandard syrups and sugar sand as by-products, which are underused. In this study, we conducted a comprehensive analysis of the physicochemical composition of these products to assess their potential for valorization. Using HPLC analysis, we measured sugar and organic acid content as well as total polyphenol content using the Folin-Ciocalteu method. Additionally, we evaluated the in vitro digestibility using the TIM-1 model. We showed that the composition of ropy and buddy downgraded syrups is comparable to that of standard maple syrup, whereas sugar sand\'s composition is highly variable, with carbohydrate content ranging from 5.01 mg/g to 652.89 mg/g and polyphenol content ranging from 11.30 µg/g to 120.95 µg/g. In vitro bioaccessibility reached 70% of total sugars for all by-products. Organic acid bioaccessibility from sugar sand and syrup reached 76% and 109% relative to standard maple syrup, respectively. Polyphenol bioaccessibility exceeded 100% during digestion. This can be attributed to favorable extraction conditions, the breakdown of complex polyphenol forms and the food matrix. In conclusion, our study demonstrates that sugar sand and downgraded maple syrups exhibit digestibility comparable to that of standard maple syrup. Consequently, they hold potential as a source of polyphenols, sugar or organic acids for applications such as industrial fermentation or livestock feeds.

Detecting overexpression of cancer biomarkers is an excellent tool for diagnostic/prognostic and follow-up of patients with cancer or their response to treatment. This work illustrates the relevance of interrogating the levels of T-cell immunoglobulin and mucin domain 1 (TIM-1) protein as a diagnostic/prognostic biomarker of high-prevalence breast and lung cancers by using an amperometric disposable magnetic microparticles-assisted immunoplatform. The developed method integrates the inherent advantages of carboxylic acid-functionalized magnetic beads (HOOC-MBs) as pre-concentrator support and the amperometric transduction at screen-printed carbon electrodes (SPCEs). The immunoplatform involves a sandwich-type immunoassay assembled on HOOC-MBs through the specific capture/labeling of TIM-1 using capture antibodies and horseradish peroxidase (HRP)-conjugated biotinylated detection antibodies as biorecognition elements. The magnetic immunoconjugates were confined onto the working electrode (WE) surface of the SPCEs for amperometric detection using the hydroquinone/hydrogen peroxide/HRP (HQ/H2O2/HRP) redox system. The method allows the selective detection of TIM-1 protein over the 87-7500 pg mL-1 concentration range in only 45 min, with a limit of detection of 26 pg mL-1. The developed bioplatform was successfully applied to the analysis of breast and lung cancer cell extracts, providing the first quantitative results of the target glycoprotein in these types of samples.

Marburg virus (MARV) has been a major concern since its first outbreak in 1967. Although the deadly BSL-4 pathogen has been reported in few individuals with sporadic outbreaks following 1967, its rarity commensurate the degree of disease severity. The virus has been known to cause extreme hemorrhagic fever presenting flu-like symptoms (as implicated in COVID-19) with a 90% case fatality rate (CFR). After a number of plausible evidences, it has been observed that the virus usually originates from African fruit bat, Rousettus aegyptiacus, who themselves do not indicate any signs of illness. Thus, efforts have been made in the recent years for a universal treatment of the infection, but till date, no such vaccine or therapeutics could circumvent the viral pathogenicity. In an attempt to formulate a vaccine design computationally, we have explored the entire proteome of the virus and found a strong correlation of its glycoprotein (GP) in receptor binding and subsequent role in infection progression. The present study, explores the MARV glycoprotein GP1 and GP2 domains for quality epitopes to elicit an extended immune response design potential vaccine construct using appropriate linkers and adjuvants. Finally, the chimeric vaccine wass evaluated for its binding affinity towards the receptors via molecular docking and molecular dynamics simulation studies. The rare, yet deadly zoonotic infection with mild outbreaks in recent years has flustered an alarming future with various challenges in terms of viral diseases. Thus, our study has aimed to provide novel insights to design potential vaccines by using the predictive framework.