After myocardial infarction (MI), extensive remodeling of extracellular matrix contributes to scar formation and preservation of hemodynamic function. On the other hand, adverse and excessive ...extracellular matrix remodeling leads to fibrosis and impaired function. The present study investigates the role of the small leucine-rich proteoglycan biglycan during cardiac extracellular matrix remodeling and cardiac hemodynamics after MI.
Experimental MI was induced in wild-type (WT) and bgn(-/0) mice by permanent ligation of the left anterior descending coronary artery. Biglycan expression was strongly increased at 3, 7, and 14 days after MI in WT mice. bgn(-/0) mice showed increased mortality rates after MI as a result of frequent left ventricular (LV) ruptures. Furthermore, tensile strength of the LV derived from bgn(-/0) mice 21 days after MI was reduced as measured ex vivo. Collagen matrix organization was severely impaired in bgn(-/0) mice, as shown by birefringence analysis of Sirius red staining and electron microscopy of collagen fibrils. At 21 days after MI, LV hemodynamic parameters were assessed by pressure-volume measurements in vivo to obtain LV end-diastolic pressure, end-diastolic volume, and end-systolic volume. bgn(-/0) mice were characterized by aggravated LV dilation evidenced by increased LV end-diastolic volume (bgn(-/0), 111+/-4.2 microL versus WT, 96+/-4.4 microL; P<0.05) and LV end-diastolic pressure (bgn(-/0), 24+/-2.7 versus WT, 18+/-1.8 mm Hg; P<0.05) and severely impaired LV function (EF, bgn(-/0), 12+/-2% versus WT, 21+/-4%; P<0.05) 21 days after MI.
Biglycan is required for stable collagen matrix formation of infarct scars and for preservation of cardiac hemodynamic function.
GVHD is a major complication following allogeneic hematopoietic SCT, and is associated with substantial morbidity and mortality. Based on the results of our previous clinical study with females ...treated with human chorionic gonadotropin (hCG) as preconditioning therapy for in vitro fertilization, we hypothesized that low-dose hCG stimulates indoleamine-2,3-dioxygenase (IDO), IL 10 and regulatory T cells (Treg), thereby suppressing clinical manifestations of chronic GVHD. Active chronic GVHD localized at skin, subcutaneous tissue, joints or gastrointestinal tract that was refractory or intolerant to glucocorticoid therapy improved substantially in 12 of 20 patients treated with hCG for 8 weeks (off-label), enabling a glucocorticoid dose reduction of 28% (average). Twelve of 19 patients with chronic GVHD of the skin responded to hCG therapy with a reduction of 25% (average) in their total skin score. HCG treatment increased IDO expression at median by sevenfold in peripheral mononuclear cells and IL10 levels in serum up to twofold at median from the pretreatment baseline. Further, an expansion of the Treg cell population was measured in one patient, which is also associated with the induction of tolerance. This novel application of low-dose hCG was well tolerated and is of clinical interest for GVHD treatment.
Over the years, pipelines have been the most economic medium for transporting crude oil to production and distribution facilities in the Niger Delta area of Nigeria. However, damages to the pipelines ...in this area by interdiction have hampered the continuous flow of crude oil to the facilities. Consequently, the revenue of the government dwindles, and the environment is severely degraded. This study assesses the economic and environmental impacts of pipeline interdiction in the Niger Delta region. Data from National oil spills detection and response agency, Nigeria is used to map spatial distribution of oil spills using Kernel Density Estimation with Geographic Information System. Literature was assessed to synthesize the historical, socioeconomic, and environmental impacts of oil spills and pipeline interdiction. Soil samples were collected from study area to determine the types of hydrocarbon pollutants and their concentrations in comparison with uncontaminated sites in the area. Results show that the range of concentrations of total petroleum hydrocarbon (TPH) for the impacted soil (IMP) was 17.27–58.36 mg/kg; remediated soil (RS) was 11.73–50.78 mg/kg which were higher than the concentrations of 0.68 mg/kg in the control samples (CS). Polycyclic aromatic hydrocarbons (PAH) concentrations were in the range of 0.43–77.54 mg/kg for IMP, 0.42–10.65 mg/kg for RS, against CS value of 0.49 mg/kg while BTEX ranged between 0.02 – 0.38 mg/kg for IMP, 0.01–2.7 for RS against CS value of 0.01. The values of the PAH were higher than the limits of the Department of Petroleum Resources, Nigeria. This study also revealed that pipeline interdiction has affected the livelihood of the inhabitants of the study area and the revenue of the Nigerian government. The major hotspots for oil spills in the Niger Delta region are Bayelsa, Rivers and Delta states.
Environmental degradation, Oil spills, Pipeline transport interdiction, Economic impact assessment, Oil exploration.
Background. Acute liver injury is a life-threatening condition with disparate aetiology. Swift and adequate interdisciplinary treatment is essential to assure the best possible outcomes in these ...patients. Investigations to identify the cause of the condition and the implementation of quick and appropriate treatment can be lifesaving. Case Presentation. In October 2022, an otherwise healthy 66-year-old male presented at the University Hospital Essen with acute liver injury following an inclisiran injection for hypercholesterinaemia. Four weeks following admission, the patient fully recovered after initially receiving short-term cortisol therapy and open albumin (OPAL) dialysis, and the indices of liver, kidney, and coagulation function were normal at discharge. Conclusion. This is to our knowledge the first reported acute liver injury due to an inclisiran injection. Cortisol in combination with OPAL dialysis is an effective method for the treatment of acute liver injury caused by inclisiran injury, and in this case, it led to a near-complete reversal of the acute liver injury at the time of discharge.
At the dawn of the third millennium, cancer has become the bane of twenty-first century man, and remains a predominant public health burden, affecting welfare and life expectancy globally. Spinal ...osteogenic sarcoma, a primary spinal malignant tumor, is a rare and challenging neoplastic disease to treat. After the conventional therapeutic modalities of chemotherapy, radiation and surgery have been exhausted, there is currently no available alternative therapy in managing cases of spinal osteosarcoma. The defining signatures of tumor survival are characterised by cancer cell ability to stonewall immunogenic attrition and apoptosis by various means. Some of these biomarkers, namely immune-checkpoints, have recently been exploited as druggable targets in osteosarcoma and many other different cancers. These promising strides made by the use of reinvigorated immunotherapeutic approaches may lead to significant reduction in spinal osteosarcoma disease burden and corresponding reciprocity in increase of survival rates. In this review, we provide the background to spinal osteosarcoma, and proceed to elaborate on contribution of the complex ecology within tumor microenvironment giving arise to cancerous immune escape, which is currently receiving considerable attention. We follow this section on the tumor microenvironment by a brief history of cancer immunity. Also, we draw on the current knowledge of treatment gained from incidences of osteosarcoma at other locations of the skeleton (long bones of the extremities in close proximity to the metaphyseal growth plates) to make a case for application of immunity-based tools, such as immune-checkpoint inhibitors and vaccines, and draw attention to adverse upshots of immune-checkpoint blockers as well. Finally, we describe the novel biotechnique of CRISPR/Cas9 that will assist in treatment approaches for personalized medication.
The present study focuses on using jackfruit seed waste (JSW) for bioremediation of heavy toxic metals from water. The fruit is abundantly grown in India and Far East countries and produces myriad ...tons of seeds. A simple procedure is developed in the laboratory by thermally activating JSW by orthophosphoric acid at 500 °C. Surface morphology, porosity, and structural analyses of the resultant biochar were conducted. The activated biochar was applied for batch adsorption of several heavy metal ions: Fe(III), Cd(II), Cu(II), Pb(II), and Mn(VII) at pH 7. The average heavy metal uptake by activated JSW biochar is 76.4 mg g
−1
, 79.4 mg g
−1
, 97.9 mg g
−1
, 79.9 mg g
−1
, and 79.8 mg g
−1
for Fe(III), Pb(II), Cu(II), Cd(II), and Mn(VII), respectively. The experimental conditions were optimized to remove heavy metals at neutral pH. The adsorption process was exothermic, and Langmuir and pseudo-second-order kinetic study models were best fitted. The observation was in close agreement with the experimental data. Thermal and structural characterization of biochar at post-adsorption analyses was conducted. The study has distinguished features of simplicity, cost-effectiveness, and viability compared to many of the literature-reported biomass waste.
Graphical abstract
Abstract Background Heart transplantation is the criterion standard for treating end-stage heart failure. Male sex of both the donor organ and the recipient is advantageous for survival, possibly ...owing to hemodynamic or immunologic reasons. The effect of sex mismatch on long-term survival in male heart transplant recipients is less known. Patients and Methods In this prospective single-center study, we reviewed follow-up data for 57 sex-mismatched and 179 sex-matched men who underwent orthotopic heart transplantation between 1990 and 2002. Results Median survival was significantly shorter in the sex-mismatched group (8.1 vs 12.9 years; P < .04). Subgroup analysis revealed that this was even more pronounced in male heart recipients with coronary artery disease (2.4 vs 12.9 years; P < .001). Female donor organs were significantly smaller (left ventricular end-diastolic diameter 49 vs 51 mm; P < .05), and recipients more often experienced clinically relevant episodes of cellular rejection during the first 3 months posttransplantation (International Society for Heart and Lung Transplantation grade 3, 5.6% vs 3.1%; P < .001). Global left ventricular function, and immunosuppressive and inflammatory parameters did not differ. Conclusion In male orthotopic heart transplant recipients, sex mismatch is associated with adverse outcome owing to increased number and severity of episodes of graft rejection.
A blue kidney, although very rare, can be encountered upon a live kidney donor. Literature has shown hemosiderin deposits, lipofuscin pigment, and melanosis as possible reasons. We report on a ...37-year-old woman who wished to donate a kidney to her husband. The donor's preoperative biochemistry and imaging tests showed normal renal function. During the laparoscopic left kidney nephrectomy, the kidney was observed to be blue in color. Perioperatively, Doppler ultrasonography was used to rule out vascular reasons, and a wedge biopsy was performed. The other kidney was also explored, and it turned out to be blue as well. Histopathological analysis showed melanosis in the tubules without malignity or pathologic changes in the glomeruli, the interstitium, or the vessels. Even though some causes of blue kidney may result in impairment of the renal function, after the necessary tests show no signs of malignity and functional impairment, a blue-colored kidney may be suitable for transplantation.
Abstract Background Intrahepatic cholangiocarcinoma (ICC) is not a widely accepted indication for orthotopic liver transplantation (OLT). The present study describes our institutional experience with ...patients who underwent transplantation for ICC as well as those with ICC who underwent transplantation with the incorrect diagnosis of hepatocellular carcinoma (HCC). Patients and Methods Data corresponding to ICC patients were reviewed for the purposes of this study. Patients with hilar cholangiocarcinoma and incidentally found ICC after OLT for benign diseases were excluded from further consideration. Results Among the 10 patients, 6 underwent transplantation before 1996 and 4 after 2001. Those who underwent transplantation in the early period had a preoperative diagnosis of inoperable ICC (n = 4) and ICC in the setting of primary sclerosing cholangitis (n = 2). In the latter period the subjects had a diagnosis of HCC in cirrhosis (n = 3) or recurrent ICC after an extended right hepatectomy (n = 1). Median survival was 25.3 months for the whole series and 32.2 months (range, 18–130 months) when hospital mortality was excluded (n = 3). Four patients are currently alive after 30, 35, 42, and 130 months post-OLT, respectively. Two patients died of tumor recurrence at 18 and 21 months post-OLT, respectively. One-, 3-, and 5-year survival rates were 70%, 50%, and 33%, respectively. Conclusions The role of OLT in the setting of ICC may be re-evaluated in the future under strict selection criteria and with prospective multicenter randomized studies. Potential candidates to be included are those with liver cirrhosis and no hilar involvement who meet the Milan criteria for HCC.
Tissue protein expression of IMP3 is emerging as a promising prognostic factor in renal cell carcinoma (RCC). The most commonly used immunohistochemical (IHC) antibody has been criticized for its low ...specificity. In addition, blood levels of IMP3 have not yet been analyzed in RCC. Therefore, we compared the prognostic performance of two different IMP3 IHC antibodies and assessed the prognostic relevance of IMP3 plasma levels in RCC. IMP3 levels were assessed in an overall number of 425 RCC (344× clear cell ccRCC, 63× papillary pRCC, 18× chromophobe chRCC) patients in three partly overlapping cohorts. Plasma IMP3 concentrations were determined by ELISA in 98 RCC (79× ccRCC, 15× pRCC, 4× chRCC) patients and 20 controls. IMP3 mRNA expression levels were analyzed in 73 frozen tissue samples (55× ccRCC, 12× pRCC, 6× chRCC), while protein expressions were assessed in 366 FFPE samples (294× ccRCC, 56× pRCC, 16× chRCC) using the M3626 and N‐19 antibodies. IMP3 plasma and mRNA expression levels were significantly higher in patients compared to controls and in high‐grade compared to low‐grade tumors. In addition, IMP3 plasma and tissue protein levels (by M3626) were higher and IMP3 mRNA expression levels tended to be higher in patients with distant metastasis. Multivariate analyses in clear cell RCC revealed high IMP3 plasma concentration and mRNA expression as independent predictors of disease‐specific survival. IMP3 immunostainings by M3626 but not by N‐19 were independently associated with poor overall and disease‐specific survival. High plasma and tissue levels of IMP3 are independently associated with poor RCC prognosis. The applied antibody significantly impacts the prognostic performance of analysis. IMP3 analysis may improve risk‐stratification of RCC patients and therefore could help to optimize therapeutic and follow‐up decisions.
What's new?
Current techniques are unable to predict which renal‐cell carcinoma (RCC) patients will develop recurrence or metastasis after surgery. While tissue expression of IMP3 is a promising prognostic factor and therapeutic target in RCC, it requires invasive sampling. In this study, the authors found that preoperative circulating IMP3 levels are independently associated with poor survival in RCC. In addition, they found that the anti‐IMP3 antibody M3626 is superior to N‐19 in terms of prognostic performance. This approach may improve risk‐stratification of RCC patients, and could therefore help to optimize therapeutic planning and follow‐up.
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