Identification and verification of feature biomarkers associated with immune cells in recurrent pregnancy loss.

OBJECTIVE: The aim of this study was to investigate the causes, diagnostic markers, and treatment methods for recurrent pregnancy loss (RPL) using bioinformatics approaches. MATERIALS AND METHODS: Bioinformatics methods were utilized to analyze gene expression databases to identify key genes and modules associated with RPL. Weighted gene co-expression network analysis (WGCNA) was employed to identify gene sets related to maternal-fetal immunity. Gene set variation analysis (GSVA) and protein-protein interaction networks were used to explore signaling pathways and molecular interactions in RPL. Immune cell infiltration was assessed using single-sample gene set enrichment analysis (ssGSEA). RESULTS: Thirteen genes were identified as potential diagnostic markers, some of which were involved in placental amino acid transport, glucose absorption, and reactive oxygen species production. Several gene sets related to protein transport, steroid synthesis, and glycosaminoglycan degradation were found to be associated with RPL. Immune cell infiltration analysis found that CD56bright NK cells and monocytes showed significantly increased infiltration in RPL and were associated with key hub genes. The validation of hub genes, including PCSK5, CCND2, SLC5A3, RASAL1, MYZAP, MFAP4, and P2RY14, as potential diagnostic markers, showed promising value. CONCLUSIONS: This study contributes to a better understanding of the etiology of RPL and potential diagnostic markers. The identified immune-related gene sets, signaling pathways, and immune cell infiltrations provide valuable insights for future research and therapeutic advancements in RPL.

Spontaneous Resolution of Ear Lidding in Newborns: A Prospective Observational Cohort Study.

ABSTRACT: Ear lidding is a cosmetic outer ear shape deformity commonly observed in newborns. Although lidding is considered a benign condition, psychological concerns such as bullying and depression have been observed in older children supporting correction of the condition. Nonsurgical correction of lidding using molding and splinting techniques has become increasingly popular, achieving successful outcomes in the majority of cases. Spontaneous resolution of the condition has also been reported in the literature however there is minimal prospective data available on the natural progression of ear lidding. In our case series of 11 closely followed newborns, we aimed to characterize the natural progression and resolution of lidding. Ten consecutive newborns participated in the observation plan and all 10 had complete spontaneous resolution of lidding within an average of 40 days. One other newborn's parents self-selected to have molding and splinting treatment. These results suggest that cosmetic treatment for less severe cases of ear lidding may be unnecessary as they have the potential to resolve on their own. Future research in this area could include controlled study designs and more work is needed to identify, which infants will require treatment. Our study may provide helpful reassurance to families and physicians that many newborns may see complete resolution of lidding without intervention.

[Epidemiological characteristics of Brucella species isolated from different regions of the world using the MLVA genotyping].

Objective: To study the molecular-epidemiological characteristics of Brucella species isolated from different countries, using the multiple locus tandem-repeat (MLVA) analysis. Methods: Eleven variable-number tandem-repeat (VNTR) loci were selected. VNTR strains of Brucella isolated from 48 different countries in 1953-2013, were analyzed by using the BioNumerics software. Unweighted Paired Arithmetic Average method was used to cluster and draw phylogenetic tree as well as the minimum spannin. Results: The evolutionary relationship of Brucella phylogenetic tree was consistent with the classical biological typing method. However, the Brucella suis biovar 5 strains were different from the other Brucella suis biovars 1, 2, 3 and 4. Brucella ceti strains were divided into two parts and different from each other. Worldwide epidemics of brucellosis were emerged from 2005 to 2008 under the MLVA11 Orsay analysis. China has been a brucellosis-prone regions, with Brucella melitensis as the main epidemic Brucella species, followed by Brucella abortus. Brucella suis was mainly identified in the southern provinces, but Brucella canis was mainly found in dogs. No human cases were found. Conclusion: Molecular-epidemiological characteristics of the Brucella strains were related to factors as time, region and hosts of isolation, which are important to setting up prevention and control programs on brucellosis.

RETRACTED: Aberrant Sialylation in Cancer Pathology and Metastasis, a Putative Drug Target Candidate

The article entitled "Aberrant Sialylation in Cancer Pathology and Metastasis, a Putative Drug Target Candidate", by Lu D.Y., Lu T.R., Xu B., Varki A., Huang M., Zhu H., Shen Y., Yarla N.S., has been retracted on the request of the co-authors Dr. Ajit Varki, Ming Huang, Hong Zhu and Ying Shen available at: Anticancer Agents Med Chem. 2018; 18(14): 1952-1961. http://www.eurekaselect.com/165282. The Corresponding Author Dr. Da-Yong Lu has included the name of the co-author Dr. Ajit Varki, Dr. Nagendra Yarla, Ming Huang, Hong Zhu and Ying Shen without their consent and the manuscript has been published in the journal Anti-Cancer Agents in Medicinal Chemistry (ACAMC). Kindly see Bentham Science Policy on Article retraction at the link given below: https://benthamscience.com/journals/anti-cancer-agents-in-medicinal-chemistry/editorial-policies/). Submission of a manuscript to the respective journals implies that all authors have read and agreed to the content of the Copyright Letter or the Terms and Conditions. As such this article represents a severe abuse of the scientific publishing system. Bentham Science Publishers takes a very strong view on this matter and apologizes to the readers of the journal for any inconvenience this may cause.

Broadband reflective lens in visible band based on aluminum plasmonic metasurface.

We demonstrate a flat optical lens based on plasmonic reflectarray metasurface, which consists of a planar array of hyperbolic-shaped aluminum (Al) nanoantenna separated from an Al ground plane by a SiO2 spacer. The gradual change in the width of the Al nanoantenna enables unique broadband (400-700 nm) to focus on the visible band because of its hyperbolic reflection-phase profile. The focal length of metalens is quickly decreased with the increase of wavelength in the short wavelength region (400-550 nm), compensating the chromatic aberration in traditional lenses. In long wavelength region (550-700 nm), the focal length has only a slight change, thereby minimizing chromatic aberration. Furthermore, the proposed metalens creates a small focal spot beyond diffraction limit, while maintaining high focusing efficiency. Our method of simple and anisotropic nanoantenna is used to realize wide phase tuning range offers a novel strategy to design braodband metalens, and our metalens has widespread applications in compact camera, telescope, and microscope.

MiR-181b modulates EGFR-dependent VCAM-1 expression and monocyte adhesion in glioblastoma.

Tumor-associated macrophages (TAMs) originate as circulating monocytes, and are recruited to gliomas, where they facilitate tumor growth and migration. Understanding the interaction between TAM and cancer cells may identify therapeutic targets for glioblastoma multiforme (GBM). Vascular cell adhesion molecule-1 (VCAM-1) is a cytokine-induced adhesion molecule expressed on the surface of cancer cells, which is involved in interactions with immune cells. Analysis of the glioma patient database and tissue immunohistochemistry showed that VCAM-1 expression correlated with the clinico-pathological grade of gliomas. Here, we found that VCAM-1 expression correlated positively with monocyte adhesion to GBM, and knockdown of VCAM-1 abolished the enhancement of monocyte adhesion. Importantly, upregulation of VCAM-1 is dependent on epidermal-growth-factor-receptor (EGFR) expression, and inhibition of EGFR effectively reduced VCAM-1 expression and monocyte adhesion activity. Moreover, GBM possessing higher EGFR levels (U251 cells) had higher VCAM-1 levels compared to GBMs with lower levels of EGFR (GL261 cells). Using two- and three-dimensional cultures, we found that monocyte adhesion to GBM occurs via integrin α4ß1, which promotes tumor growth and invasion activity. Increased proliferation and tumor necrosis factor-α and IFN-γ levels were also observed in the adherent monocytes. Using a genetic modification approach, we demonstrated that VCAM-1 expression and monocyte adhesion were regulated by the miR-181 family, and lower levels of miR-181b correlated with high-grade glioma patients. Our results also demonstrated that miR-181b/protein phosphatase 2A-modulated SP-1 de-phosphorylation, which mediated the EGFR-dependent VCAM-1 expression and monocyte adhesion to GBM. We also found that the EGFR-dependent VCAM-1 expression is mediated by the p38/STAT3 signaling pathway. Our study suggested that VCAM-1 is a critical modulator of EGFR-dependent interaction of monocytes with GBM, which raises the possibility of developing effective and improved therapies for GBM.

Outcomes in HIV-infected patients who develop tuberculosis after starting antiretroviral treatment in Malawi.

A retrospective review was conducted of patients starting antiretroviral treatment (ART) at Mzuzu Central Hospital, Malawi, to identify those who developed tuberculosis (TB) within 6 months of commencing ART and document their treatment outcomes. Of 2933 patients, 22 (0.75%) developed active TB, 17 (77%) of whom had commenced ART as a result of unexplained weight loss and/or fever. Of those who developed TB, 41% successfully completed anti-tuberculosis treatment, with lower survival probabilities than patients who did not develop TB. Easier methods are needed to diagnose TB in human immunodeficiency virus-infected patients and to prevent patients from developing TB while on ART.

Expression and immunohistochemical localization of aquaporin-1 in male reproductive organs of the mouse.

Aquaporin-1 (AQP-1), a six-transmembrane domain protein, is found to be responsible for water transport. The purpose of this study was to investigate the expression of AQP-1 mRNA and protein in the testis, epididymis, vas deferens, ventral prostate, and seminal vesicle from mature mice by using reverse transcription polymerase chain reaction (RT-PCR) and Western blotting, and the cellular localization of AQP-1 by immunohistochemistry. RT-PCR revealed that AQP-1 mRNA was expressed in all organs we examined. Western blotting displayed a 29-kDa band and a 35- to 45-kDa band corresponding to non-glycosylated and/or glycosylated AQP-1 in those organs. The immunohistochemical evidence showed that AQP-1 was mainly located on the plasma membrane of epithelial cells of the rete testis, vas deferens, ventral prostate, seminal vesicle and the non-ciliated cells of the proximal and distal efferent ducts. However, AQP-1 was absent from spermatogenic cells lining the seminiferous epithelium and from the spermatozoa in the lumen of the distal efferent duct. These findings provide valuable information on the expression of AQP-1 in male reproductive organs and suggest that AQP-1 is involved in water transport to regulate water homeostasis in male reproductive physiology.

YC-1 attenuates LPS-induced proinflammatory responses and activation of nuclear factor-kappaB in microglia.

BACKGROUND AND PURPOSE: An inflammatory response in the central nervous system mediated by the activation of microglia is a key event in the early stages of the development of neurodegenerative diseases. LPS has been reported to cause marked microglia activation. It is very important to develop drugs that can inhibit microglia activation and neuroinflammation. Here, we investigated the inhibitory effect of YC-1, a known activator of soluble guanylyl cyclase, against LPS-induced inflammatory responses in microglia. EXPERIMENTAL APPROACH: To understand the inhibitory effects of YC-1 on LPS-induced neuroinflammation, primary cultures of rat microglia and the microglia cell line BV-2 were used. To examine the mechanism of action of YC-1, LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production, iNOS, COX-2 and cytokine expression were analyzed by Griess reaction, ELISA, Western blotting and RT-PCR, respectively. The effect of YC-1 on LPS-induced activation of nuclear factor kappa B (NF-kappaB) was studied by NF-kappaB reporter assay and immunofluorocytochemistry. KEY RESULTS: YC-1 inhibited LPS-induced production of NO and PGE2 in a concentration-dependent manner. The protein and mRNA expression of iNOS and COX-2 in response to LPS application were also decreased by YC-1. In addition, YC-1 effectively reduced LPS-induced expression of the mRNA for the proinflammatory cytokines, TNF-alpha and IL-1beta. Furthermore, YC-1 inhibited LPS-induced NF-kappaB activation in microglia. CONCLUSIONS AND IMPLICATIONS: YC-1 was able to inhibit LPS-induced iNOS and COX-2 expression and NF-kappaB activation, indicating that YC-1 may be developed as an anti-inflammatory neuroprotective agent.

Effect of anti-cancer drugs on the binding of 125I-Fibrinogen to two leukaemia cell lines in vitro.

Anti-cancer drugs may be able to inhibit tumour growth and metastasis by blocking fibrinogen- and/or fibrin-related pathways. To test this hypothesis, the effect of various anti-neoplastic drugs on the binding of 125I-Fibrinogen to two leukaemia cell lines, HL60 and P388, was investigated. All the drugs tested inhibited the binding of fibrinogen to leukaemia cells. This effect was particularly marked for drugs that act as inhibitors of protein synthesis. Since these anti-neoplastic drugs do not have anti-coagulant actions, these results provide evidence for the potential of targeting tumour fibrinogen as a new form of cancer chemotherapy.

Severity of coronary artery disease in black and white male veterans and likelihood of revascularization.

BACKGROUND: Many reports in the literature have found the use of invasive cardiac procedures in black patients to be less common than in white patients. These reports tend to have small numbers of black patients compared with white patients or rely on the information contained in claims or administrative data. METHODS AND RESULTS: Cardiac catheterization reports were reviewed in a Veterans Administration hospital that serves a large number of black patients. After review of the medical histories and hemodynamic and angiographic findings in 726 black and 734 white male veterans, data were collected to determine recommended and actual therapy. Death was assessed after a 4- to 10-year follow-up period. White patients were more likely to have significant coronary artery lesions than black patients. Multivariate analysis showed that the likelihood of patients actually having percutaneous transluminal coronary angioplasty or coronary artery bypass surgery did not differ by ethnicity when controlling for disease extent or severity. Coronary artery bypass surgery was associated with decreased mortality rates for both black and white patients. Although short-term death in blacks was not different from whites, blacks had an increased long-term risk for death. CONCLUSIONS: After coronary angiography, black veterans and white veterans appear to undergo revascularization procedures related to the severity of disease. The decreased long-term life expectancy of black men as compared with whites is not necessarily explained by the presence of or treatment for coronary artery disease in this population.

[Regeneration of HNP transgenic alfalfa plants by Agrobacterium mediated gene transfer].

Transgenic plants regenerated from cotyledons of M. sativa L. infected using Agrobacterium tumefaciens A281 with plasmid pBF649 containing a gene encoding protein of high sulfur-amino acid content (HNP) were obtained successfully. The plants grew and fertiled well in field. Cotyledon explants were better recipient for transformation of M. sativa L. Environment of suitable temperature (15 degrees C) and high humidity on high viability of the plants transplanted into soil were essential conditions.

Effects of cancer chemotherapy on the blood fibrinogen concentrations of cancer patients.

Blood fibrinogen concentrations and glutamic-pyruvic transaminase activities of 66 adult cancer inpatients (aged 22 - 70 years) were determined both before and after one or two chemotherapy regimens. The percentage of hepatoma patients with abnormal blood fibrinogen levels (< 1.5 or > 6.0 g/l) was higher (64.3% of 14 patients) than that in other cancer categories (19.2% of 52 patients). The mean blood fibrinogen concentrations of male (3.5 g/l) and female (4.5 g/l) cancer patients were higher than those previously reported for healthy humans (2.8 and 2.9 g/l, respectively). After chemotherapy, blood fibrinogen concentrations decreased in patients whose primary tumours were surgically removed (from 4.8 to 3.2 g/l) but increased (from 3.0 to 4.8 g/l) in those who did not undergo surgery. Glutamic-pyruvic transaminase activities did not appear to be related to blood fibrinogen levels. We conclude that the increase in mean blood fibrinogen levels of cancer patients is probably related to tumour growth. Different mechanisms may operate in patients with hepatoma.

Autoantibody titers to oxidized low-density lipoprotein in patients with coronary atherosclerosis.

Oxidation of low-density lipoprotein (LDL) is considered to be the initial step in the atherosclerotic process. Autoantibodies to oxidized LDL (ox-LDL) have been detected in human serum. We used an enzyme-linked immunosorbent assay technique to measure autoantibody titers in 63 normal subjects and patients with coronary artery disease. Thirty-five patients underwent coronary angiography for suspected coronary artery disease. Patients were divided into the following categories: group 1, 20 healthy young volunteers; group 2, 8 patients age-matched to the catheterization patients; group 3, 10 patients with normal coronary angiograms; and group 4, 25 patients with angiographic coronary artery disease. Autoantibody titers to ox-LDL were group 1, 0.142 +/- 0.023; group 2, 0.197 +/- 0.039; group 3, 0.183 +/- 0.038; and group 4, 0.340 +/- 0.026. There was no statistical difference among groups 1, 2, and 3, but the difference between these groups and group 4 was highly significant (p < 0.05). This study demonstrates that (1) autoantibodies to ox-LDL can be detected in normal subjects and in patients with abnormal coronary angiograms and (2) significantly higher titers of autoantibodies to ox-LDL were seen in patients with angiographic evidence of coronary artery disease.

[A clinical study of inhibition of secondary cataract with heparin].

Extracapsular cataract extraction with posterior chamber lens implantation was performed on 47 eyes with senile cataract of which 25 eyes were in the control group and 22 eyes were irrigated with heparin solution (25U/ml) in the operation, the drug group. Postoperatively, 2 eyes with hyphema were found in the drug group, but the deposition of fibrin and cells on the anterior lenticular surface and the posterior capsular opacification were significantly less than those in the control group. 3 months after the operation, the mean visual acuity in the drug group was 0.70 +/- 0.26 markedly higher than that in the control group, 0.54 +/- 0.28 (P < 0.05).

A new experimental and clinical approach of combining usage of highly active tumor-infiltrating lymphocytes and highly sensitive antitumor drugs for the advanced malignant tumor.

In recent years, tumor-infiltrating lymphocytes (TILs) have been reported to be effective for tumors in experimental and clinical research. In order to increase the therapeutical effect, we modified some steps of Rosenberg's approach: a. cold digestion with collagenase at 4 degrees C for 24 hours; b. sedimentation instead of centrifugation; c. elimination of tumor cells before the cultivation procedure. Compared with the original approach, the proliferation, activity and cytotoxicity of TILs obtained by the modified procedure were much improved. TILs' expansion-fold was greater than that with the original approach. Cytotoxicity against tumor cells was more potent. Increased TILs' subsets were CD3 and CD8 cells. Meanwhile, we took tumor cells from tumor tissues to test their in vitro chemosensitivities to different drugs in order to select highly sensitive antitumor drugs for treatment of cases with advanced tumors. According to the design of using highly active TILs and highly sensitive drugs (H & H therapy), preliminary clinical results of 50 cases showed higher response rates than those in treatment with TIL/IL2, LAK/IL2 and TIL+IL2+CTX. Less toxic side effects were observed in 14 patients.

[A cytological study of inhibition of secondary cataract with heparin].

Secondary cataract is caused primarily by migration and proliferation of fibroblasts on the posterior capsular surface after extracapsular cataract extraction. Human fetus skin fibroblast cell culture was used, by measurement of cell's life cycle, cellular DNA content, increase of cell number and density, to investigate the heparin inhibitory action on the growth of the cells. It is discovered that the growth rate of the fibroblasts is lowered in the culture medium with heparin and the inhibition takes place at the interval between G1 and S stage and at M stage of the cell's life cycle.

[Study on the influence of enzymatic digestion upon tumor-infiltrating lymphocytes].

To get a long-term culture of tumor-infiltrating lymphocytes (TILs) is very difficult. The authors have investigated some suitable enzymes, their digestive conditions such as time and temperature, which may influence the viability and cytotoxicity of TILs. The results showed that collagenase II and IV could keep viability of TILs much longer than those treated with trypsin or hyaluronidase. The digestion with collagenase II or IV at 4 degrees C for 24 hours was much less damage to viability of TILs than those treated at 37 degrees C for one hour. The TILs, which digested at 4 degrees C for 24 hours, still had cytotoxicity against autologous tumor cells as long as sixty to seventy-five days.

[Distribution of 14C labeled at dioxopiperazine or methyl morpholine group of probimane by whole body autoradiography].

Probimane (AT-2153) is a new anticancer compound. It was first developed in this Institute. It is effective against mouse tumors S37, S180, Lewis lung carcinoma, L1210 and human pulmonary adenocarcinoma heterotransplanted into nude mice. In the present work, 14C was labeled at central dioxopiperazine or methyl morpholine group of probimane 120 mg.kg-1 was injected iv in mice bearing Lewis lung carcinoma by whole body autoradiography. The results showed that probimane was broken into at least two parts: a central part and a methyl morpholine group. The central part of compound hardly penetrated through the blood-brain barrier, but accumulated in the urinary bladder. The methyl morpholine group showed a high affinity to tumor tissue and accumulated in spleen, bone and liver.