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Feathers, burdensome waste from the poultry industry, can be a cheap source of keratin, a protein with excellent physicochemical, biological, and mechanical properties. Acid and alkaline hydrolyses are usually adopted for isolation of keratin from its natural resources. This study aimed at assessing the statistically significant effect of input variables in the alkaline hydrolysis of keratin from chicken feathers on the process yield and on the molecular weight of peptides obtained. The effect of the volume ratio of 1M NaOH to the feathers’ mass, the hydrolysis time, and the shaking speed of the reaction mixture on the process yield were analyzed. The use of statistical analysis at the design step of experiment allowed reducing the trial number from 27 to 9. Among the input variables analyzed, only the volume ratio of 1M NaOH to the feathers’ mass had a significant effect on the process yield, while none of them significantly affected the molecular weight of the peptides obtained. All hydrolysates were dominated by two peptides’ fractions, with molecular weights of ca. 130 and 250 kDa, and mixture of many peptides of weight close to 10 kDa and smaller. Alkaline hydrolysis of feather keratin yielded protein hydrolysates soluble over a wide pH range.

Background: The efficacy of SARS-CoV-2 vaccination among kidney transplant recipients (KTR) is low. The main goal of this study was to analyze factors that may influence the humoral response to vaccination. Methods: We analyzed the titer magnitude of IgG antibodies directed against spike (S)-SARS-CoV-2 antigen after the second dose of the mRNA vaccine in 142 infection naïve KTR (83 men, i.e., 58.4%) with a median age (IQR) of 54 (41–63), and 36 respective controls without chronic kidney disease. mRNA-1273 or BNT162b2 were applied in 26% and 74% of KTR, respectively. Results: S-specific immune response (seroconversion) was seen in 73 (51.41%) of KTR, and in all controls 36 (100%). Independent predictors of no response were elder age, shorter transplantation vintage, and a more than two-drug immunosuppressive protocol. In subgroup analyses, the seroconversion rate was highest among KTR without MMF/MPS treatment (70%), treated with no more than two immunosuppressants (69.2%), treated without corticosteroid (66.7%), younger patients aged <54 years (63.2%), and those vaccinated with the mRNA-1273 vaccine (62.16%). The independent predictors of higher S-antibody titer among responders were younger age, treatment with no more than two immunosuppressants, and the mRNA-1273 vaccination. Conclusions: Our study confirmed a low rate of seroconversion after vaccination with the mRNA vaccine in KTR. The major modifiable determinants of humoral response were the composition of the immunosuppressive protocol, as well as the type of vaccine. The latter could be taken into consideration when initial vaccination as well as booster vaccination is considered in KTR.

Vaccination against COVID-19 in patients with end-stage renal disease (ESRD) on replacement therapy and kidney transplant recipients (KTRs) is particularly important due to the high mortality rate. Here, we tested the local and systemic immunity to the novel Pfizer BioNTech (BNT162b2) messenger RNA (mRNA) in ESRD, KTR patients, and healthy individuals (150 subjects). The ESRD group was divided into: hemodialysis (HD) and peritoneal dialysis (PD). We investigated the local and systemic immunity based on anti-N (nucleoprotein) and anti-S (spike1/2) Immunoglobulin A (IgA) and Immunoglobulin G (IgG) antibodies, respectively. Additionally, we performed an Interferon gamma (IFN-γ) release test Interferon-gamma release assay (IGRA) to monitor the cellular component of vaccine response. The control group had the highest level of anti-S IgG antibodies (153/2,080 binding antibody units (BAU)/ml) among all analyzed patients after the 1st and 2nd dose, respectively. The HD group (48/926 BAU/ml) had a diminished antibody level compared to PD (93/1,607 BAU/ml). Moreover, the seroconversion rate after the 1st dose was lower in HD than PD (56% vs. 86%). KTRs had extremely low seroconversion (33%). IgA-mediated immunity was the most effective in the control group, while other patients had diminished IgA production. We observed a lower percentage of vaccine responders based on the IFN-γ level in all research participants (100% vs. 85% in control, 100% vs. 80% in PD, 97% vs. 64% in HD). 63% of seropositive KTRs had a positive IGRA, while 28% of seronegative patients produced IFN-γ. Collectively, PD patients had the strongest response among ESRD patients. Two doses of the Pfizer vaccine are ineffective, especially in HD and KTRs. A closer investigation of ESRD and KTRs is required to set the COVID-19 vaccine clinical guidance.

During pregnancy in larger mammals, the maternal immune system must tolerate the fetus for months while resisting external infection. This tolerance is facilitated by immunological communication between the fetus and the mother, which is mediated by Major Histocompatibility Complex I (MHC I) proteins, by leukocytes, and by the cytokines secreted by the leukocytes. Fetal-maternal immunological communication also supports pregnancy by inducing physiological changes in the mother. If the mother “misunderstands” the signal sent by the fetus during pregnancy, the fetus will be miscarried or delivered preterm. Unlike any other maternal organ, the placenta can express paternal antigens. At parturition, paternal antigens are known to be expressed in cows and may be expressed in horses, possibly so that the maternal immune system will reject the placenta and help to expel it. This review compares fetal-maternal crosstalk that is mediated by the immune system in three species with pregnancies that last for nine months or longer: humans, cattle, and horses. It raises the possibility that immunological communication early in pregnancy may prepare the mother for successful expulsion of fetal membranes at parturition.

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease, characterized by impaired wound repair, tissue remodeling and fibrosis. Immune system may participate in the development and progression of the disease as indicated by altered activity in IPF sufferers. This study investigates the immune response to the BNT162b2 COVID-19 vaccine in patients with IPF compared to healthy controls, with a particular focus on evaluation of antibody responses, interferon-gamma release, cytokine profiling and a broad panel of immune cell subpopulations. IPF patients without prior exposure to SARS-CoV-2 had undetectable levels of anti-N IgG antibodies, highlighting their lack of previous infection. After vaccination, IPF patients showed a significant increase in anti-S1 IgG and IgA antibodies, though their levels were lower compared to healthy controls and convalescent IPF patients. Additionally, IPF patients exhibited altered proportions of regulatory T cells (Tregs) and effector T lymphocytes (Teffs) before and after vaccination. Specifically, IPF patients had higher percentages of Tregs with a Th2 phenotype and Th17 Tregs, along with reduced proportions of Th1/17 Tregs. Teffs in IPF patients showed a decrease in Th1-like and Th2-like populations after vaccination. Moreover, IPF patients demonstrated elevated populations of cytotoxic T lymphocytes (Tc) before vaccination and increased levels of γδ Tc cells throughout the study. Alterations in cytokine profiles were also observed, IPF patients showed higher levels of IL-6 and IL-22 compared to healthy controls. These findings suggest a distinct immune response in IPF patients to the COVID-19 vaccine, characterized by differences in antibody production, T cell differentiation and cytokine secretion compared to healthy individuals.

Introduction: The immune response to the primary (two-dose) series of mRNA COVID-19 vaccines in kidney transplant recipients (KTRs) is very weak. We conducted a longitudinal observational study to compare the humoral response to a third, additional primary dose of mRNA vaccines between infection-naïve (IN-KTRs) and previously infected KTRs (PI-KTRs). Methods: We measured the levels of anti-spike (anti-s) IgG antibodies before and 14–21 days after the third dose and, in the secondary analysis, we compared the antibody response to BNT162b2 versus mRNA-1273. The reactogenicity assessment included solicited local and systemic reactions. Results: A total of 112 KTRs were enrolled, including 83 IN-KTR and 29 PI-KTR, among whom seroconversion in anti-s antibodies after the primary two-dose vaccination was achieved in 45.78% and 100% of cases, respectively. After three months, a waning antibodies titer by 67.4% (IN-KTR) and 7.5% (PI-KTR) was observed. After the third dose of the mRNA vaccine, 71.08% (59/83) of IN-KTR and 96.5% (28/29) of PI-KTR samples were seroconverted with a median anti-s titer of 468.0 (195.0–1620.0) BAU/mL and 1629.0 (1205–1815) BAU/mL, respectively. Of those IN-KTR in whom the primary vaccination failed, 46.67% (21/45) of patients achieved seroconversion after the third dose. No serious adverse events after the third dose were reported. In strata analyses, after the third dose, 66% (40/60) of patients vaccinated with BNT162b2 and 82.6% (19/23) of patients vaccinated with mRNA-1273 seroconverted with a median anti-s titer of 384.5 (144–837) BAU/mL and 1620 (671–2040) BAU/mL, respectively. Conclusions: The use of a third dose of mRNA vaccine may be of benefit for KTR, especially for those in whom the primary vaccination failed. Vaccines with a higher dose of mRNA and a longer interval between doses of the primary vaccination, such as mRNA-1273, seem to be the preparations of choice in immunocompromised individuals.

(1) Background and Objectives: Vitamin D is implicated in the pathogenesis of Chronic Kidney Disease—Mineral and Bone Disorder (CKD-MBD) in hemodialysis (HD) patients, including the development of secondary hyperparathyroidism (SHP). While cholecalciferol supplementation is recommended for vitamin D deficiency correction, its impact on CKD-MBD remains inconsistent. The aim of this observational prospective study was to assess the effect of cholecalciferol in achieving high–normal serum 25-hydroxycholecalciferol (25(OH)D > 75 ng/mL) levels and its impact on CKD-MBD biochemical markers, including 1,25-dihydroxycholecalciferol (1,25(OH)2D) and parathormone (PTH) in HD patients. The study also evaluated the maintenance dosage required to sustain 25(OH)D levels within the 50–75 ng/mL range. (2) Materials and Methods: A total of 22 HD patients with baseline 25(OH)D levels 30–50 ng/mL received cholecalciferol (70,000 IU/week) to achieve the target serum 25(OH)D > 75 ng/mL. Baseline data on calcium, phosphate, 1–84 PTH, 25(OH)D, and 1,25(OH)2D serum levels were compared with the data when 25(OH)D > 75 ng/mL was targeted or when the highest 25(OH)D levels were noted. (3) Results: Cholecalciferol significantly improved vitamin D status in HD patients, with 73% reaching the target 25(OH)D level >75 ng/mL in a median time of 7.5 weeks, with a median total dose of 525,000 IU. This was associated with a significant rise in 1,25(OH)2D, decrease in 1–84 PTH, and no significant effect on calcium and phosphate levels. The median maintenance dose of cholecalciferol was established at 30,000 IU/week. (4) Conclusions: The findings support the use of cholecalciferol targeting high normal 25(OH)D levels to improve biochemical markers of CKD-MBD in HD patients.

The aim of this study was to analyze the waning of anti-spike (S) antibodies after mRNA vaccination against COVID-19 in maintenance dialysis patients, and to assess the safety and effectiveness of the complementary third dose. This was a prospective, longitudinal study in which we analyzed the kinetics of antibodies up to six months after a two-dose vaccination (first protocol) in infection-naïve dialysis patients (IN-Ds), previously infected dialysis patients (PI-Ds) and subjects without chronic kidney disease (the controls), as well as their humoral response to the third dose of the same mRNA vaccine (second protocol). The respective reduction in antibody titer after 3 and 6 months by 82.9% and 93.03% in IN-Ds (n = 109), 73.4% and 93.36% in PI-Ds (n = 32) and 75.5% and 88.8% in the controls (n = 20) was demonstrated. Consequently, a protective antibody titer above 141 BAU/mL was found in only 47.7% and 23.8% of IN-Ds after 3 and 6 months, respectively. After the third vaccine dose, a significant increase in antibody titer was observed in all groups, with increases by a factor of ×51.6 in IN-Ds, ×30.1 in the controls and ×8.4 in PI-Ds. The median antibody titer after the third dose differed significantly between groups, and was the highest in PI-Ds: PI-Ds, 9090 (3300–15,000) BAU/mL; the controls, 6945 (2130–11,800); IN-Ds, 3715 (1470–7325) (p < 0.001). In conclusion, we observed similar degrees of antibody waning in all patients. After 3 months, over half of the infection-naïve dialysis patients had a very low antibody titer, and almost twenty percent of them had no antibodies at all. The humoral response to the third dose was very good, raising their titer of antibodies to a higher level than those in the general population who have received the primary two-dose scheme. The results support the administration of a complementary third dose of the mRNA vaccine for dialysis patients as soon as possible.

Vitamin D deficiency and insufficiency are highly prevalent in CKD, affecting over 80% of hemodialysis (HD) patients and requiring therapeutic intervention. Nephrological societies suggest the administration of cholecalciferol according to the guidelines for the general population. The aim of the observational study was to evaluate the efficacy and safety of the therapy with a high dose of cholecalciferol in HD patients with 25(OH)D deficiency and insufficiency to reach the target serum 25(OH)D level > 30 ng/mL. A total of 22 patients (16 M), with an average age of 72.5 ± 13.03 years and 25(OH)D concentration of 13.05 (9.00–17.90) ng/mL, were administered cholecalciferol at a therapeutic dose of 70,000 IU/week (20,000 IU + 20,000 IU + 30,000 IU, immediately after each dialysis session). All patients achieved the target value > 30 ng/mL, with a mean time of 2.86 ± 1.87 weeks. In the first week, the target level of 25(OH)D (100%) was reached by 2 patients (9.09%), in the second week by 15 patients (68.18%), in the fourth week by 18 patients (81.18%), and in the ninth week by all 22 patients (100%). A significant increase in 1,25(OH)2D levels was observed during the study. However, only 2 patients (9.09%) achieved a concentration of 1,25(OH)2D above 25 ng/mL—the lower limit of the reference range. The intact PTH concentrations remained unchanged during the observation period. No episodes of hypercalcemia were detected, and one new episode of hyperphosphatemia was observed. In conclusion, our study showed that the administration of a high-therapeutic dose of cholecalciferol allowed for a quick, effective, and safe leveling of 25(OH)D concentration in HD patients.

One of the most innovative medical trends is personalized therapy, based on simple and reproducible methods that detect unique features of cancer cells. One of the good prognostic and diagnostic markers may be the miRNA family. Our work aimed to evaluate changes in selected miRNA levels in various breast cancer cell lines (MCF7, MDA-MB-231, SK-BR-3) treated with doxorubicin or cisplatin. The selection was based on literature data regarding the most commonly altered miRNAs in breast cancer (21-3p, 21-5p, 106a-5p, 126-3p, 126-5p, 155-3p, 155-5p, 199b-3p, 199b-5p, 335-3p, 335-5p). qPCR assessment revealed significant differences in the basal levels of some miRNAs in respective cell lines, with the most striking difference in miR-106a-5p, miR-335-5p and miR-335-3p—all of them were lowest in MCF7, while miR-153p was not detected in SK-BR-3. Additionally, different alterations of selected miRNAs were observed depending on the cell line and the drug. However, regardless of these variables, 21-3p/-5p, 106a, 126-3p, 155-3p and 199b-3p miRNAs were shown to respond either to doxorubicin or to cisplatin treatment. These miRNAs seem to be good candidates for markers of breast cancer cell response to doxorubicin or cisplatin. Especially since some earlier reports suggested their role in affecting pathways and expression of genes associated with the DNA-damage response. However, it must be emphasized that the preliminary study shows effects that may be highly related to the applied drug itself and its concentration. Thus, further examination, including human samples, is required.