ARS-CoV-2 was first detected in December 2019, leading to a pandemic with an estimated 5-6% mortality rate 1. Akin to SARS-CoV-1, the causative agent of the 2003 SARS outbreak, this is an enveloped betacoronavirus with protrusions of large trimeric 'spike' proteins. Receptor binding domains (RBDs) located at the tips of these spikes facilitate host cell entry via interaction with angiotensin-converting enzyme 2 (ACE2) 2. Spikes are type I transmembrane glycoproteins, formed from a single polypeptide, which transitions into a post-fusion state via cleavage into S1 (N-terminal) and S2 (C-terminal) chains following receptor binding or trypsin treatment 3. In the pre-fusion state, the apical RBD (~22 kDa) is folded down, enshrouded by the N-terminal domain (NTD) of the spike so that the receptor binding site is inaccessible until, it is assumed, an RBD stochastically swings upwards to present the ACE2 binding site 4-7. ACE2 interaction locks the RBD in the 'up' conformation, which drives conversion to the post-fusion form where the S2 subunit engages the host membrane while dispensing with S1 4,5. Neutralizing human monoclonal antibodies (mAbs) that recognize the ACE2 receptor binding site for SARS-CoV-1 and SARS-CoV-2 are generally not cross-reactive between the two viruses and are susceptible to escape mutation 8-12. Indeed, a natural mutation (Y495N) has already been identified at this site (GISAID 13 : accession ID: EPI_ISL_429783 Wienecke-Baldacchino et al.). By contrast, the CR3022 antibody (derived from a SARS-CoV-1-infected patient) cross-reacts strongly with SARS-CoV-2 (see Methods and Fig. 1) and has been shown to recognize a cryptic, conserved footprint on the RBD distinct from the binding epitope of

Our results substantiate a previous suggestion that the mtDNA 16189 variant can cause alteration of mtDNA copy number in human blood cells.

Background: Although the health benefits of vegetarian diets have been well documented among Western population, there are geographic differences of vegetarian diets and the health benefits of the Taiwanese vegetarian diet have not been studied extensively. In addition to conventional risk factors, homocysteine and high-sensitivity C-reactive protein (hs-CRP) levels have been found to predict first atherothrombotic events. We undertook this study to examine the total risk profile of Taiwanese vegetarians. Methods: A total of 198 healthy subjects (99 vegetarians and 99 omnivores) were recruited. Fasting blood samples were analyzed for glucose, cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), white blood cell count, hs-CRP and homocysteine. Results: There was no significant difference in age, body mass index, blood glucose, white blood cell count, triglyceride and HDL-C between the two groups. The vegetarian group had significantly more females (65.7 vs 46.5%); lower body weight (58.66711.13 vs 62.88712.24 kg); shorter height (159.1477.88 vs 162.53 78.14 cm); lower total cholesterol (184.74733.23 vs 202.01741.05 mg/dl); and lower LDL-C (119.63731.59 vs 135.89739.50 mg/dl). Hs-CRP was significantly lower (0.1470.23 vs 0.2370.44 mg/dl, P ¼ 0.025), whereas homocysteine was significantly higher (10.9776.69 vs 8.4472.50 mmol/l, P ¼ 0.001) in vegetarians than omnivores. Conclusions: Taiwanese vegetarians have lower total cholesterol, LDL-C and hs-CRP levels, and higher homocysteine levels than omnivores. Owing to different predictive value of each risk factor, the Taiwanese vegetarians had a better cardiovascular risk profile than omnivores. Whether the Taiwanese vegetarian diet should be supplemented with vitamin B 12 to lower serum homocysteine level remains to be addressed.

The objective of this study was to evaluate the effects of dendritic cell and cytokine-induced killer (DC-CIK) cell-based immunotherapy combined with chemotherapy on the treatment of patients with advanced colorectal cancer. We prospectively included patients with advanced colorectal cancer and assessed the efficacy of DC-CIK cell-based immunotherapy combined with chemotherapy compared to treatment with chemotherapy alone. T cell subtypes, progression-free survival (PFS), overall survival (OS), and adverse events were evaluated in each group. In total, 134 patients were included in the DC-CIK group and 121 patients were included in the control group. No significant differences were observed in the percentages of CD3(+), CD3(+)CD4(+), CD3(+)CD8(+), and NK cells after DC-CIK cell-based immunotherapy compared to before chemotherapy in the DC-CIK group. The median PFS and OS in the DC-CIK treatment group were 8.8 months (95 % CI 8.4-9.1) and 14.7 months (95 % CI 13.9-15.5), respectively, which were significantly improved compared to the PFS and OS in the control group. The frequencies of grade III and IV leukopenia (8.2 vs. 19.0 %, P = 0.011), grade III and IV anemia (3.0 vs. 9.1 %, P = 0.039), and grade III and IV thrombocytopenia (3.7 vs. 10.7 %, P = 0.029) were significantly lower in the DC-CIK group compared to the control group. DC-CIK cell-based immunotherapy could induce an immune response against colorectal cancer and prolong PFS and OS. DC-CIK cell-based immunotherapy combined with chemotherapy had a significant benefit in terms of survival in patients with colorectal cancer compared to chemotherapy alone.

BackgroundUrethral reconstruction is one of the great surgical challenges for urologists. A cell-based tissue-engineered urethra may be an alternative for patients who have complicated long strictures and need urethral reconstruction. Here, we demonstrated the feasibility of using autologous urine-derived stem cells (USCs) seeded on small intestinal submucosa (SIS) to repair a urethral defect in a rabbit model.MethodsAutologous USCs were obtained and characterized, and their capacity to differentiate into urothelial cells (UCs) and smooth muscle cells (SMCs) was tested. Then, USCs were labeled with PKH67, seeded on SIS, and transplanted to repair a urethral defect. The urethral defect model was surgically established in New Zealand white male rabbits. A ventral urethral gap was created, and the urethral mucosa was completely removed, with a mean rabbit penile urethra length of 2 cm. The urethral mucosal defect was repaired with a SIS scaffold (control group: SIS with no USCs; experimental group: autologous USC-seeded SIS; n = 12 for each group). A series of tests, including a retrograde urethrogram, histological analysis, and immunofluorescence, was undertaken 2, 3, 4, and 12 weeks after the operation to evaluate the effect of the autologous USCs on urethral reconstruction.ResultsAutologous USCs could be easily collected and induced to differentiate into UCs and SMCs. In addition, the urethral caliber, speed of urothelial regeneration, content of smooth muscle, and vessel density were significantly improved in the group with autologous USC-seeded SIS. Moreover, inflammatory cell infiltration and fibrosis were found in the control group with only SIS, but not in the experimental autologous USC-seeded SIS group. Furthermore, immunofluorescence staining demonstrated that the transplanted USCs differentiated into UCs and SMCs in vivo.ConclusionsAutologous USCs can be used as an alternative cell source for cell-based tissue engineering for urethral reconstruction.

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Non-obstructive azoospermia is the most challenging type of male infertility. Stem cell based therapy provides the potential to enhance the recovery of spermatogenesis following cancer therapy. Bone marrow-derived mesenchymal stem cells (BMSCs) possess the potential to differentiate or trans-differentiate into multi-lineage cells, secrete paracrine factors to recruit the resident stem cells to participate in tissue regeneration, or fuse with the local cells in the affected region. In this study, we tested whether spermatogenically-induced BMSCs can restore spermatogenesis after administration of an anticancer drug. Allogeneic BMSCs were co-cultured in conditioned media derived from cultured testicular Sertoli cells in vitro, and then induced stem cells were transplanted into the seminiferous tubules of a busulfan-induced azoospermatic rat model for 8 weeks. The in vitro induced BMSCs exhibited specific spermatogonic gene and protein markers, and after implantation the donor cells survived and located at the basement membranes of the recipient seminiferous tubules, in accordance with what are considered the unique biological characteristics of spermatogenic stem cells. Molecular markers of spermatogonial stem cells and spermatogonia (Vasa, Stella, SMAD1, Dazl, GCNF, HSP90α, integrinβ1, and c-kit) were expressed in the recipient testis tissue. No tumor mass, immune response, or inflammatory reaction developed. In conclusion, BMSCs might provide the potential to trans-differentiate into spermatogenic-like-cells, enhancing endogenous fertility recovery. The present study indicates that BMSCs might offer alternative treatment for the patients with azoospermatic infertility after cancer chemotherapy.

BackgroundColorectal cancer (CRC) is a major burden of public health and healthcare worldwide. Microbiota has been suggested in promoting chronic inflammation in the intestine which, in turn, promotes tumor development. This study focuses on possible correlations of human papillomavirus (HPV) infection with proinflammatory Stat3 signaling activities and the resulting levels of its downstream proinflammatory cytokine IL-17 in CRC patients.MethodsHPV was examined using HPV Genotyping Chip technology and constitutively active Stat3 (p-Stat3) and IL-17 levels were tested using immunohistochemistry (IHC) in paraffin-embedded cancerous and adjacent normal tissues (ANT) from a cohort of 95 CRC patients. Correlation analyses were performed between HPV infection and clinicopathological characteristics, Stat3 activities and IL-17 levels among these CRC patients.ResultsThree major findings were observed: (1) HPV infection existed in a high rate of CRC cases (48.4%, 46/95), of which 45 cases (45/46, 97.8%) were high-risk HPV16-positive and only one case was HPV53-positive. (2) HPV infection correlated with poorer clinical stages (III+IV) of CRC. (3) HPV infection strongly correlated with both constitutively higher Stat3 activities (P<0.01) and higher IL-17 levels (P<0.01) only in CRC tissues but not in ANT tissues.ConclusionsHPV infection is common in CRC patients suggesting potentially preventive effectiveness of HPV vaccination among high-risk young individuals. We have for the first time revealed a tri-lateral relationship among HPV infection, constitutive Stat3 activity and IL-17 level, whose collaborative act may orchestrate a proinflammatory microenvironment in the colorectum that, in turn, may promote carcinogenesis and possibly facilitate progression of CRC.