Non-alcoholic fatty liver disease (NAFLD), the leading cause of chronic liver disease in Western countries, has been identified as a possible risk factor for COVID-19 severity. However, the immunological mechanisms by which NAFLD exacerbates COVID-19 remain unknown. Transforming growth factor-beta 1 (TGF-β1) has an important immunomodulatory and pro-fibrotic role, which has already been described in NAFLD. However, the role of TGF-β1 in COVID-19 remains unclear, and could also be the pathophysiology link between these two conditions. The aim of this case-control study was to analyze the expression of TGF-β1 in COVID-19 patients depending on the presence of NAFLD and COVID-19 severity. Serum TGF-β1 concentrations were measured in 60 hospitalized COVID-19 patients (30 with NAFLD). NAFLD was associated with higher serum TGF-β1 concentrations that increased with disease severity. Admission TGF-β1 concentrations showed good discriminative accuracy in predicting the development of critical disease and COVID-19 complications (need for advanced respiratory support, ICU admission, time to recovery, development of nosocomial infections and mortality). In conclusion, TGF-β1 could be an efficient biomarker for predicting COVID-19 severity and adverse outcomes in patients with NAFLD.

BACKGROUND: Heterotopic ossification (HO) is the formation of osseous tissue outside the skeleton. HO in malignant tumors of the digestive tract is extremely rare, as is ossification in metastatic lesions from HO-negative digestive tract tumors. Regarding the pathogenesis of HO, two theories have been proposed. The first is that the osteoblastic metaplasia of tumor cells (driven by the epithelial-mesenchymal transition, EMT) results in HO, and the second is that factors secreted by cancer cells lead to the metaplasia of stromal pluripotent cells into osteoblasts. However, the osteogenic mechanisms remain unclear.
METHODS: An 83-year-old Japanese woman underwent low anterior rectal resection for rectal cancer before presentation at our institution, in June 2018. The final diagnosis was stage IIB rectal adenocarcinoma (T4aN0M0). Histological examination did not reveal HO in the primary tumor. Thirteen months after the operation, a solitary metastatic lesion in the brain 20 mm in size and a solitary metastatic lesion in a right axillary lymph node 20 mm in size were diagnosed. The patient was treated with gamma-knife therapy for the brain metastasis. One month later, she was referred to our institution. She underwent lymph node resection. Histological examination revealed that most portions of the affected lymph node were occupied by metastatic tumor cells and that central necrosis and four small ossified lesions without an osteoblast-like cell rim were present in the peripheral region. Immunohistochemical analysis showed tumor cells positive for BMP-2, osteonectin, osteocalcin, AE1/AE3, TGF-β1, Gli2, Smad2/3, and CDX2 and negative for nestin, CD56, and CK7.
CONCLUSIONS: This is the first English case report of HO in a metachronous metastatic lymph node after the curative resection of HO-negative rectal cancer. Unlike HO lesions in past reports, the HO lesion did not show peripheral osteoblast-like cells, and the immunohistochemical findings indicated that the present case resulted from the EMT.

BACKGROUND: Epidemiological studies of adult glioma have identified genetic and environmental risk factors, but much remains unclear. The aim of the current study was to evaluate anthropometric, disease-related, and prediagnostic immune-related factors for relationship with glioma risk.
METHODS: We conducted a nested case-control study among the intervention arm of the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening Trial. One hundred and twenty-four glioma cases were identified and each matched to four controls. Baseline characteristics were collected at enrollment and were evaluated for association with glioma status. Serum specimens were collected at yearly intervals and were analyzed for immune-related factors including TGF-β1, TNF-α, total IgE, and allergen-specific IgE. Immune factors were evaluated at baseline in a multivariate conditional logistic regression model, along with one additional model that incorporated the latest available measurement.
RESULTS: A family history of glioma among first-degree relatives was associated with increased glioma risk (OR = 4.41, P = .002). In multivariate modeling of immune factors at baseline, increased respiratory allergen-specific IgE was inversely associated with glioma risk (OR for allergen-specific IgE > 0.35 PAU/L: 0.59, P = .03). A logistic regression model that incorporated the latest available measurements found a similar association for allergen-specific IgE (P = .005) and showed that elevated TGF-β1 was associated with increased glioma risk (P-value for trend <.0001).
CONCLUSIONS: The results from this prospective prediagnostic study suggest that several immune-related factors are associated with glioma risk. The association observed for TGF-β1 when sampling closer to the time of diagnosis may reflect the nascent brain tumor\'s feedback on immune function.

Transforming growth factor (TGF)-β1 contributed to angiotensin II (Ang II)-mediated collagen accumulation after myocardial infarction (MI). The present study aimed to investigate the association of genetic variant of TGF-β1 gene with the risk of MI. The present study recruited a total of 530 MI patients and 651 healthy controls. The genomic DNA was extracted and subjected into polymerase chain reaction (PCR) and Sanger sequencing. The present study indicated that TGF-β1 -913G/C polymorphism was associated with increased risk for MI under the co-dominant, dominant and allelic models. The increased risk effect was also evident among the females, younger subjects (age < 60 years), smokers, non-drinkers and individuals with hypertension. Additionally, the present study observed significant differences among cases and controls in terms of total cholesterol (TC). In conclusion, TGF-β1 -913G/C polymorphism is associated with increased risk for MI. TGF-β1 -913G/C polymorphism may be a potential prognostic biomarker for MI.

Phyllanthus muellerianus (Family Euphorbiaceae) is a shrub, which is widely distributed in West Africa and employed traditionally as a wound-healing agent especially in Ghana. The aim of the study was to determine the in vivo wound-healing activity of aqueous aerial part extract of P. muellerianus (PLE) and its major isolate, geraniin. Excision and incision wound models were used to determine the wound-healing activity. Wounds were treated with PLE (0.25, 0.5, and 1% w/w) and geraniin (0.1, 0.2, and 0.4% w/w) aqueous creams. PLE and geraniin significantly (p < 0.001) increased wound contraction rate and hydroxyproline production compared to untreated wounds. Histological studies of wound tissues showed high levels of fibroblasts and increased collagen content and cross-linking in PLE and geraniin-treated wound tissues. Immuno-histochemical investigations revealed high levels of TGF-β1 in PLE and geraniin-treated wound tissues compared to the untreated wound tissues. Tensile strength of incised wounds was significantly (p < 0.05) high in PLE and geraniin-treated wounds. PLE (0.1-100 μg/mL) significantly (p < 0.001) reduce LDH release from HaCaT-keratinocytes compared to the untreated cells. PLE and geraniin possess wound healing and cytoprotective effect.

We present herein a case report style article on a rare advanced triple-negative breast cancer (TNBC) patient with 6-month disease-free interval, and 10-month overall survival. Our results demonstrate that the poor clinical outcome of this patient was associated with pronounced, more than fivefold higher, overexpression of both cFOS and TGF-β1 proteins in its metastatic nodal tissue extracts, when compared with the values of the two non-TNBC controls (with \'zero\' disease-free interval and overall survival). This original observation suggests, for the first time, that both the cFOS and TGF-β1 may be considered as a pair of biomarkers for an early assessment of poor prognosis for TNBC patients. The possible clinical implication of this observation is discussed.

BACKGROUND: Genetic susceptibility plays a key role in the development of nasopharyngeal carcinoma (NPC) and in fact the disease presents with an unusually high incidence in certain regions of the world like North Africa. We investigated the association between polymorphism of the Transforming growth factor-β1 (TGF-β1) and risk of NPC in North Africa. TGF-β1 is a multifunctional cytokine that acts as both a tumor suppressor and a stimulator of cancer development; it has been shown to influence risk of numerous other carcinomas including lung, breast and prostate cancer.
METHODS: TGF-β1 polymorphisms C-509T and T869C were studied in a large North African sample of 384 NPC cases and 361 controls, matched for age, sex and urban or rural residence in childhood. Genotypes were determined using polymerase chain reaction-restriction fragment length polymorphism.
RESULTS: No association was observed between individual single nucleotide polymorphisms or their haplotypes and NPC susceptibility (for TGF-β1 C-509T: OR = 0.74; 95 % CI 0.46 - 1.18; for TGF-β1 T869C: OR = 0.86; 95 % CI 0.56 - 1.31), even when the samples were stratified by age, gender and TNM stage.
CONCLUSIONS: Contrary to what has been observed in Asian samples, in our North African sample, the TGF-β1 C-509T and T869C polymorphisms did not substantially influence NPC susceptibility.

BACKGROUND: Transforming growth factor-β1 (TGF-β1) reportedly acts as a tumor suppressor in tumorigenesis. However, little is known as to how TGF-β1 concentrations change prior to the development of hepatocellular carcinoma (HCC) in humans. We examined the association between the serum TGF-β1 concentrations and death from HCC to determine whether the serum TGF-β1 can be a predictor of incident HCC.
METHODS: We conducted a nested case-controlled study of participants in the Japan Collaborative Cohort Study for Evaluation of Cancer Risk. We used a conditional logistic regression analysis to estimate the adjusted relative risks (aRRs) of death from HCC according to the serum TGF-β1 concentrations among 1940 participants including 83 patients with HCC and 1857 controls matched for age, sex, and hepatitis C virus (HCV)-antibody seropositivity.
RESULTS: When serum TGF-β1 was modelled as a continuous variable, the aRR of death from HCC associated with a decrement of 7.9ng/mL (one standard deviation) in the serum TGF-β1 concentrations was 2.3 (95% CI 1.7-3.0, P<0.001) for all the subjects. The area under the receiver operating characteristic curve for the serum TGF-β1 concentrations was 0.78 (P<0.05).
CONCLUSIONS: Our finding suggests that TGF-β1 serves as a predictor for HCC.

OBJECTIVE: Pre-eclampsia (PE) is a disorder of pregnancy characterized by high blood pressure and proteinuria. Transforming growth factor beta-1 (TGF-β1) is an important replicated PE candidate gene, and few studies have evaluated the direct association of TGF-β polymorphisms and risk to PE. The aim of this study was to investigate the association between three SNPs of TGF-β1 and serum level of this cytokine in PE patients and controls.
METHODS: In this study the polymorphisms of the TGF-β1 gene at the coding region, and positions 29T→C (Leu 10 Pro), 74G→C (Arg 25 Pro) and 788C→T (Thr 263 Ile) were studied in 123 PE and 120 normal subjects using PCR-restriction fragment length polymorphism PCR-(RFLP) and amplification refractory mutation system (ARMS)-PCR methods. Moreover, serum TGF-β1 was determined by enzyme-linked immunosorbent assay (ELISA) technique.
RESULTS: At positions 74G→C and 29T→C the genotypes and allele frequencies showed no significant differences between PE patients and normal controls (P=0.3 and P=0.5 respectively). While in the case of position 788C→T both genotypes and allele frequencies were significantly different between PE patients and controls (P=0.02). Haplotype analysis on three polymorphic sites showed no significant differences between PE and control individuals (P=0.8). TGC and CGC haplotypes were the most frequent in both studied groups. The mean serum TGF-β1 level was significantly higher (62.73ng/ml) in PE patients compared with pregnant (47.01ng/ml) and non-pregnant (40.68ng/ml) control groups (P=0.0001).
CONCLUSIONS: The results of this study suggest that TGF-β1 gene 788C→T polymorphism is an important factor mediating the casual pathway of preeclampsia.