BACKGROUND: Many patients with coronavirus disease 2019 (COVID-19) suffer multiple organ dysfunctions. However, whether patients develop dyslipidemia is unknown. OBJECTIVE: In this study, we aimed to investigate the pathological alterations of low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), and total cholesterol (TC) in COVID-19 patients and their relationships with the disease severity. METHODS: A retrospective study was performed to examine serum levels of LDL-c, HDL-c, and TC on 597 COVID-19 patients (mild: 394; severe, 171; critical: 32) who were hospitalized in our center between February 1 and March 3, 2020. Age-and gender-matched normal subjects (n 5 50) who had routine laboratory lipid tests between October 1 and November 1, 2019 in our center were included as the control group. RESULTS: LDL-c and TC levels were significantly lower in COVID-19 patients as compared with normal subjects (P , .001). There were significant and gradual decreases in levels of LDL-c (median (IQR) in mg/dL, mild:

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In this retrospective study, we evaluated the levels of a series of serum biomarkers in coronavirus disease 2019 (COVID-19) patients (mild: 131; severe: 98; critical: 23). We found that there were significant increases in levels of human epididymis protein 4 (HE4)

The pandemic of coronavirus disease 2019 (COVID-19) has become a global threat to public health. Functional impairments in multiple organs have been reported in COVID-19 including lungs, heart, kidney, liver, brain and vascular system. Patients with metabolic-associated preconditions such as hypertension, obesity and diabetes are susceptible to experience severe symptoms. The recent emerging evidence of coagulation disorders in COVID-19 suggests that vasculopathy appears to be an independent risk factor promoting disease severity and mortality of affected patients. We have recently found that the decreased levels of low-density lipoprotein cholesterols (LDL-c) correlate with disease severity in COVID-19 patients, indicating pathological interactions between dyslipidemia and vasculopothy in COVID-19 patients. However, this clinical manifestation has been unintentionally underestimated by physicians and scientific communities. As metabolic-associated morbidities are generally accompanied with endothelial cell (EC) dysfunctions, these pre-existing conditions may make ECs more vulnerable to SARS-CoV-2 attack. In this mini-review, we summarize the metabolic and vascular manifestations of COVID-19 with an emphasis on the association between changes in LDL-c levels and the development of severe symptoms as well as the pathophysiologic mechanisms underlying the synergistic effect of LDL-c and SARS-CoV-2 on EC injuries and vasculopathy.

The control principles behind robust cyclic regeneration of hair follicles (HFs) remain unclear. Using multi-scale modeling, we show that coupling inhibitors and activators with physical growth of HFs is sufficient to drive periodicity and excitability of hair regeneration. Model simulations and experimental data reveal that mouse skin behaves as a heterogeneous regenerative field, composed of anatomical domains where HFs have distinct cycling dynamics. Interactions between fast-cycling chin and ventral HFs and slow-cycling dorsal HFs produce bilaterally symmetric patterns. Ear skin behaves as a hyper-refractory domain with HFs in extended rest phase. Such hyper-refractivity relates to high levels of BMP ligands and WNT antagonists, in part expressed by ear-specific cartilage and muscle. Hair growth stops at the boundaries with hyper-refractory ears and anatomically discontinuous eyelids, generating wave-breaking effects. We posit that similar mechanisms for coupled regeneration with dominant activator, hyper-refractory, and wave-breaker regions can operate in other actively renewing organs.DOI: http://dx.doi.org/10.7554/eLife.22772.001

Transforming growth factor-β (TGF-β)/Smad signaling plays a key role in excessive fibrosis and keloid formations. Smad7 is a negative feedback regulator that prevents activation of TGF-β/Smad signaling. However, the regulatory mechanism for Smad7 in the keloid pathogenic process remains elusive. Here, we show that expression of TIEG1 is markedly higher in keloid fibroblasts, whereas protein, mRNA, and promoter activity levels of Smad7 are decreased. When TIEG1 was knocked down with small interfering RNA, both the promoter activity and protein expression of Smad7 were increased, whereas collagen production and the proliferation, migration, and invasion of keloid fibroblasts were decreased. In contrast, TIEG1 overexpression led to a decrease in Smad7 expression and Smad7 promoter activity. Upon TGF-β1 stimulation, TIEG1 promoted Smad2 phosphorylation by down-regulating Smad7. Luciferase reporter assays and chromatin immunoprecipitation assays further showed that TIEG1 can directly bind a GC-box/Sp1 site located between nucleotides -1392 and -1382 in the Smad7 promoter to repress Smad7 promoter activity. Taken together, these findings show that TIEG1 is highly expressed in human keloids and that it directly binds and represses Smad7 promoter-mediated activation of TGF-β/Smad2 signaling, thus providing clues for development of TIEG1 blocking strategies for therapy or prophylaxis of keloids.

Background The feasibility of carotid artery intima-media thickness (C-IMT), an established cardiovascular disease marker, as a cardiac risk marker in mucopolysaccharidosis (MPS) patients was explored. Objectives To determine if C-IMT is abnormal in MPS versus unaffected controls, and if C-IMT correlates with coronary artery diameter in MPS. Material and methods Measurements of C-IMT via neck ultrasound and echocardiographic parameters, including coronary artery diameters, were obtained from MPS and control patients, and compared. Results Sixteen MPS subjects (6 MPS I, 6 MPS II, 2 MPS III, 1 MPS VI, 1 MPS VII) and sixteen age, ethnicity, and gender-matched controls were enrolled. Median MPS and control subject ages were 8.3 ± 4.5 and 8.6 ± 4.3 years, respectively (p = 0.73). Mean MPS and control C-IMTs were 0.54 ± 0.070 and 0.48 ± 0.034 mm (p = 0.0029). No differences in left main, left anterior descending, or right coronary artery diameters were seen between MPS and controls. A significant proportion of MPS subjects had mitral insufficiency (14/16; p=0.0002), aortic insufficiency (10/16; p=0.0021), and left ventricular dilatation (7/16, p=0.037) versus controls. C-IMT did not correlate significantly with age, height, weight, coronary measurements, or duration of treatment. Conclusion C-IMT in MPS patients is increased compared to matched controls, likely reflective of arterial intima-medial glycosaminoglycan accumulation. MPS subjects demonstrated a high percentage of left-sided valvular insufficiency and ventricular dilatation. Additional studies should be performed in MPS patients to determine if C-IMT correlates with arterial elasticity, biomarkers of vascular dysfunction, and higher risk of cardiovascular events.

The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) plays a crucial role in mediating viral entry into host cells. However, whether it contributes to pulmonary hyperinflammation in patients with coronavirus disease 2019 is not well known. In this study, we developed a spike protein–pseudotyped (Spp) lentivirus with the proper tropism of the SARS‐CoV‐2 spike protein on the surface and determined the distribution of the Spp lentivirus in wild‐type C57BL/6J male mice that received an intravenous injection of the virus. Lentiviruses with vesicular stomatitis virus glycoprotein (VSV‐G) or with a deletion of the receptor‐binding domain (RBD) in the spike protein [Spp (∆RBD)] were used as controls. Two hours postinfection (hpi), there were 27‐75 times more viral burden from Spp lentivirus in the lungs than in other organs; there were also about 3‐5 times more viral burden from Spp lentivirus than from VSV‐G lentivirus in the lungs, liver, kidney, and spleen. Deletion of RBD diminished viral loads in the lungs but not in the heart. Acute pneumonia was observed in animals 24 hpi. Spp lentivirus was mainly found in SPC+ and LDLR+ pneumocytes and macrophages in the lungs. IL6, IL10, CD80, and PPAR‐γ were quickly upregulated in response to infection in the lungs as well as in macrophage‐like RAW264.7 cells. Furthermore, forced expression of the spike protein in RAW264.7 cells significantly increased the mRNA levels of the same panel of inflammatory factors. Our results demonstrated that the spike protein of SARS‐CoV‐2 confers the main point of viral entry into the lungs and can induce cellular pathology. Our data also indicate that an alternative ACE2‐independent viral entry pathway may be recruited in the heart and aorta.