Factors predicting difficult spinal block: A single centre study.

BACKGROUND AND AIMS: Several factors determine the success of dural puncture. We aimed to assess the association of first puncture success and number of attempts with characteristics of the patient, provider, technique and equipment. MATERIAL AND METHODS: This prospective, observational study was performed in 1647 adult patients undergoing surgery under spinal anesthesia. Patient characteristics, anatomical landmarks, spinal bony deformity, provider experience, technique, skin punctures, needle redirections, subarachnoid space depth, and complications, if any, were noted. Difficult dural puncture was assessed by first puncture success and number of attempts (skin punctures plus needle redirections) required for successful needle placement. RESULTS: First puncture success was obtained in 872 (52.9%) patients. Failed dural puncture occurred in 4 (0.2%) of 1647 patients. Multivariate logistic regression analysis revealed that longer distance from C7 vertebral spine to tip of coccyx (P = 0.04), lower subarachnoid space depth (P = 0.001), good quality of bony landmarks (P = 0.001) and absence of crowded spine (P = 0.02) were associated with first puncture success. Male gender, poor or no spinal landmarks, presence of bony deformity and lower level of provider's experience predicted increased number of attempts for successful dural puncture. CONCLUSION: First puncture success of spinal block was influenced only by patient's anatomical factors, whereas the number of attempts required for successful block were predicted by both provider and patient factors.

Bcp1 Is the Nuclear Chaperone of Rpl23 in Saccharomyces cerevisiae.

Eukaryotic ribosomes are composed of rRNAs and ribosomal proteins. Ribosomal proteins are translated in the cytoplasm and imported into the nucleus for assembly with the rRNAs. It has been shown that chaperones or karyopherins responsible for import can maintain the stability of ribosomal proteins by neutralizing unfavorable positive charges and thus facilitate their transports. Among 79 ribosomal proteins in yeast, only a few are identified with specific chaperones. Besides the classic role in maintaining protein stability, chaperones have additional roles in transport, chaperoning the assembly site, and dissociation of ribosomal proteins from karyopherins. Bcp1 has been shown to be necessary for the export of Mss4, a phosphatidylinositol 4-phosphate 5-kinase, and required for ribosome biogenesis. However, its specific function in ribosome biogenesis has not been described. Here, we show that Bcp1 dissociates Rpl23 from the karyopherins and associates with Rpl23 afterward. Loss of Bcp1 causes instability of Rpl23 and deficiency of 60S subunits. In summary, Bcp1 is a novel 60S biogenesis factor via chaperoning Rpl23 in the nucleus.

Bone breaking infections - A focus on bacterial and mosquito-borne viral infections.

The recent global resurgence of arthritogenic alphaviruses, including Ross River, chikungunya, and dengue, highlights an urgency for the development of therapeutic strategies. Currently, dengue represents the most rapidly transmitting mosquito-borne viral disease worldwide. By contracting bone breaking diseases, patients experience devastating clinical manifestations involving muscle pain and bone loss. The bone self-repair and regeneration mechanisms can be damaged by the presence of viruses and bacteria. The rapid establishment of dengue epidemic and the severity of bacterial and viral infections affecting the bone stress the urgent need of developing effective interventions. Herein, we review current knowledge on bone breaking infections, covering both bacterial and mosquito-borne viral ones. The mechanisms exploited by these diseases to significantly affect the bone, including interferences with self-repair and regeneration routes, were discussed. In the final section, challenges for future research aimed to treat and prevent bacterial and mosquito-borne bone-breaking infections have been outlined.

Stem cell therapies for myocardial infarction in clinical trials: bioengineering and biomaterial aspects.

Cardiovascular disease remains the leading cause of death and disability in advanced countries. Stem cell transplantation has emerged as a promising therapeutic strategy for acute and chronic ischemic cardiomyopathy. The current status of stem cell therapies for patients with myocardial infarction is discussed from a bioengineering and biomaterial perspective in this review. We describe (a) the current status of clinical trials of human pluripotent stem cells (hPSCs) compared with clinical trials of human adult or fetal stem cells, (b) the gap between fundamental research and application of human stem cells, (c) the use of biomaterials in clinical and pre-clinical studies of stem cells, and finally (d) trends in bioengineering to promote stem cell therapies for patients with myocardial infarction. We explain why the number of clinical trials using hPSCs is so limited compared with clinical trials using human adult and fetal stem cells such as bone marrow-derived stem cells.

The synthesis, characterization and in vivo study of mineral substituted hydroxyapatite for prospective bone tissue rejuvenation applications.

Minerals substituted apatite (M-HA) nanoparticles were prepared by the precipitation of minerals and phosphate reactants in choline chloride-Thiourea (ChCl-TU) deep eutectic solvent (DESs) as a facile and green way approach. After preparation of nanoparticles (F-M-HA (F=Fresh solvent)), the DESs was recovered productively and reprocess for the preparation of R-M-HA nanoparticles (R=Recycle solvent).The functional groups, phase, surface texture and the elemental composition of the M-HA nanoparticles were evaluated by advance characterization methods. The physicochemical results of the current work authoritative the successful uses of the novel (ChCl-TU) DESs as eco-friendly recuperate and give the medium for the preparation of M-HA nanoparticles. Moreover, the as-synthesized both M-HA nanoparticles exhibit excellent biocompatibility, consisting of cell co-cultivation and cell adhesion, in vivo according to surgical implantation of Wistar rats.

Anti-Inflammatory Potential of Ethyl Acetate Fraction of Moringa oleifera in Downregulating the NF-κB Signaling Pathway in Lipopolysaccharide-Stimulated Macrophages.

In the present investigation, we prepared four different solvent fractions (chloroform, hexane, butanol, and ethyl acetate) of Moringa oleifera extract to evaluate its anti-inflammatory potential and cellular mechanism of action in lipopolysaccharide (LPS)-induced RAW264.7 cells. Cell cytotoxicity assay suggested that the solvent fractions were not cytotoxic to macrophages at concentrations up to 200 µg/mL. The ethyl acetate fraction suppressed LPS-induced production of nitric oxide and proinflammatory cytokines in macrophages in a concentration-dependent manner and was more effective than the other fractions. Immunoblot observations revealed that the ethyl acetate fraction effectively inhibited the expression of inflammatory mediators including cyclooxygenase-2, inducible nitric oxide synthase, and nuclear factor (NF)-κB p65 through suppression of the NF-κB signaling pathway. Furthermore, it upregulated the expression of the inhibitor of κB (IκBα) and blocked the nuclear translocation of NF-κB. These findings indicated that the ethyl acetate fraction of M. oleifera exhibited potent anti-inflammatory activity in LPS-stimulated macrophages via suppression of the NF-κB signaling pathway.

Generation of pluripotent stem cells without the use of genetic material.

Induced pluripotent stem cells (iPSCs) provide a platform to obtain patient-specific cells for use as a cell source in regenerative medicine. Although iPSCs do not have the ethical concerns of embryonic stem cells, iPSCs have not been widely used in clinical applications, as they are generated by gene transduction. Recently, iPSCs have been generated without the use of genetic material. For example, protein-induced PSCs and chemically induced PSCs have been generated by the use of small and large (protein) molecules. Several epigenetic characteristics are important for cell differentiation; therefore, several small-molecule inhibitors of epigenetic-modifying enzymes, such as DNA methyltransferases, histone deacetylases, histone methyltransferases, and histone demethylases, are potential candidates for the reprogramming of somatic cells into iPSCs. In this review, we discuss what types of small chemical or large (protein) molecules could be used to replace the viral transduction of genes and/or genetic reprogramming to obtain human iPSCs.

Recent developments in ß-cell differentiation of pluripotent stem cells induced by small and large molecules.

Human pluripotent stem cells, including human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), hold promise as novel therapeutic tools for diabetes treatment because of their self-renewal capacity and ability to differentiate into beta (ß)-cells. Small and large molecules play important roles in each stage of ß-cell differentiation from both hESCs and hiPSCs. The small and large molecules that are described in this review have significantly advanced efforts to cure diabetic disease. Lately, effective protocols have been implemented to induce hESCs and human mesenchymal stem cells (hMSCs) to differentiate into functional ß-cells. Several small molecules, proteins, and growth factors promote pancreatic differentiation from hESCs and hMSCs. These small molecules (e.g., cyclopamine, wortmannin, retinoic acid, and sodium butyrate) and large molecules (e.g. activin A, betacellulin, bone morphogentic protein (BMP4), epidermal growth factor (EGF), fibroblast growth factor (FGF), keratinocyte growth factor (KGF), hepatocyte growth factor (HGF), noggin, transforming growth factor (TGF-α), and WNT3A) are thought to contribute from the initial stages of definitive endoderm formation to the final stages of maturation of functional endocrine cells. We discuss the importance of such small and large molecules in uniquely optimized protocols of ß-cell differentiation from stem cells. A global understanding of various small and large molecules and their functions will help to establish an efficient protocol for ß-cell differentiation.

Retraction of "Cisplatin-Loaded Graphene Oxide/Chitosan/Hydroxyapatite Composite as a Promising Tool for Osteosarcoma-Affected Bone Regeneration".

[This retracts the article DOI: 10.1021/acsomega.8b02090.].

Human embryonic stem cells cultured on hydrogels grafted with extracellular matrix protein-derived peptides with polyethylene glycol joint nanosegments.

Human pluripotent stem cells (hPSCs) can be proliferated on completely synthetic materials under xeno-free cultivation conditions using biomaterials grafted with extracellular matrix protein (ECM)-derived peptides. However, cell culture biomaterials grafted with ECM-derived peptides must be prepared using a high concentration of peptide reaction solution (e.g. 1000 µg/ml), whereas the ECM concentration of the ECM-coated surface for hPSC culture is typically 5 µg/ml. We designed a polyethylene glycol (PEG) joint nanosegment (linker) to be used between base cell culture biomaterials and bioactive ECM-derived peptides to enhance the probability of contact between ECM-derived peptides and cell binding receptors of hPSCs. Vitronectin-derived peptides with glycine joint nanosegments (GCGG) were conjugated onto poly (vinyl alcohol-co-itaconic acid) hydrogels via PEG joint nanosegments, and human embryonic stem cells (hESCs) were cultivated on these hydrogels. hESCs could successfully be cultivated on hydrogels while maintaining their pluripotency and differentiation potential to differentiate into cells that are induced from three germ layers in vitro and in vivo, where only a 50 µg/ml ECM-derived peptide concentration was used when the PEG joint nanosegments were introduced into peptides that were grafted onto hydrogel surfaces. The joint nanosegments between bioactive peptides and base cell culture biomaterials were found to contribute to efficient hESC attachment and proliferation.

Direct, indirect, post-infection damages induced by coronavirus in the human body: an overview.

Background: Severe acute respiratory syndrome Coronavirus-2 invades the cells via ACE2 receptor and damages multiple organs of the human body. Understanding the pathological manifestation is mandatory to endure the rising post-infection sequel reported in patients with or without comorbidities. Materials and methods: Our descriptive review emphasises the direct, indirect and post-infection damages due to COVID-19. We have performed an electronic database search according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines with selective inclusion and exclusion criteria. Results: The included studies substantiated the extensive damages in the multiple organs due to direct and indirect consequences of COVID-19. After an apparent recovery, the prolonged presentation of the symptoms manifests as post-COVID that can be related with persisting viral antigens and dysregulated immune response. Conclusion: A few of the symptoms of respiratory, cardiovascular, and neuropsychiatric systems that persist or reappear as post-COVID manifestations. Vaccination and preventive programs will effectively reduce the prevalence but, the post-COVID, a multisystem manifestation, will be a significant tribulation to the medical profession. However, the issue can be managed by implementing public health programs, rehabilitation services, and telemedicine virtual supports to raise awareness and reduce panic.

Deep vein thrombosis and euvolemic hyponatremia in a hypothyroid patient.

Hypothyroidism is a procoagulant state; hypothyroid females have greater risk of DVT than hypothyroid males. We present a case of primary hypothyroidism who presented with euvolemic hyponatremia and DVT that required thyroxine replacement and correction of hyponatremia. This highlights that hypothyroidism can present as euvolemic hyponatremia and deep vein thrombosis.

Correction to Cisplatin-Loaded Graphene Oxide/Chitosan/Hydroxyapatite Composite as a Promising Tool for Osteosarcoma-Affected Bone Regeneration.

[This corrects the article DOI: 10.1021/acsomega.8b02090.].

Glycyrrhizic Acid: A Natural Plant Ingredient as a Drug Candidate to Treat COVID-19.

The total number of cumulative cases and deaths from the COVID-19 pandemic caused by SARS-CoV-2 is still increasing worldwide. Although many countries have actively implemented vaccination strategies to curb the epidemic, there is no specific efficient therapeutic drug for this virus to effectively reduce deaths. Therefore, the underappreciated macromolecular compounds have become the spotlight of research. Furthermore, the medicinal compounds in plants that provide myriad possibilities to treat human diseases have become of utmost importance. Experience indicates that Traditional Chinese medicine effectively treats SARS and has been used for treating patients with COVID-19 in China. As one of the world's oldest herbal remedies, licorice is used for treating patients with all stages of COVID-19. Glycyrrhizic acid (GA), the main active compound in licorice, has been proven effective in killing the SARS virus. Meanwhile, as a natural plant molecule, GA can also directly target important protein structures of the SARS-CoV-2 virus and inhibit the replication of SARS-CoV-2. In this review, we summarized the immune synergy of GA and its potential role in treating COVID-19 complications. Besides, we reviewed its anti-inflammatory effects on the immune system and its positive effects in cooperation with various drugs to fight against COVID-19 and its comorbidities. The purpose of this review is to elucidate and suggest that GA can be used as a potential drug during COVID-19 treatment.

Utilization of Carica papaya latex on coating of SPIONs for dye removal and drug delivery.

Latex, a milky substance found in a variety of plants which is a natural source of biologically active compounds. In this study, Latex was collected from raw Carica papaya and was characterized using UV-Vis, FTIR and GC-MS analyses. Super Paramagnetic Iron Oxide Nanoparticles (SPIONs) were synthesized, coated with C. papaya latex (PL-Sp) and characterized using UV-Vis, FT-IR, SEM-EDX, XRD, VSM and Zeta potential analyses. SPIONs and latex coated SPIONs (PL-Sp) were used in batch adsorption study for effective removal of Methylene blue (MB) dye, where (PL-Sp) removed MB dye effectively. Further the PL-Sp was used to produce a nanoconjugate loaded with curcumin and it was characterized using UV-Vis spectrophotometer, FT-IR, SEM-EDX, XRD, VSM and Zeta potential. It showed a sustained drug release pattern and also found to have good antibacterial and anticancer activity.

Stem Cell Therapy in Dengue Virus-Infected BALB/C Mice Improves Hepatic Injury.

Extensive clinical efforts have been made to control the severity of dengue diseases; however, the dengue morbidity and mortality have not declined. Dengue virus (DENV) can infect and cause systemic damage in many organs, resulting in organ failure. Here, we present a novel report showing a tailored stem-cell-based therapy that can aid in viral clearance and rescue liver cells from further damage during dengue infection. We administered a combination of hematopoietic stem cells and endothelial progenitor cells in a DENV-infected BALB/c mouse model and found that delivery of this cell cocktail had improved their liver functions, confirmed by hematology, histopathology, and next-generation sequencing. These stem and progenitor cells can differentiate into target cells and repair the damaged tissues. In addition, the regime can regulate endothelial proliferation and permeability, modulate inflammatory reactions, enhance extracellular matrix production and angiogenesis, and secrete an array of growth factors to create an enhanced milieu for cell reparation. No previous study has been published on the treatment of dengue infection using stem cells combination. In conclusion, dengue-induced liver damage was rescued by administration of stem cell therapy, with less apoptosis and improved repair and regeneration in the dengue mouse model.

Corrigendum: Stem Cell Therapy in Dengue Virus-Infected BALB/C Mice Improves Hepatic Injury.

[This corrects the article DOI: 10.3389/fcell.2021.637270.].

Potential Factors Influencing Repeated SARS Outbreaks in China.

Within last 17 years two widespread epidemics of severe acute respiratory syndrome (SARS) occurred in China, which were caused by related coronaviruses (CoVs): SARS-CoV and SARS-CoV-2. Although the origin(s) of these viruses are still unknown and their occurrences in nature are mysterious, some general patterns of their pathogenesis and epidemics are noticeable. Both viruses utilize the same receptor-angiotensin-converting enzyme 2 (ACE2)-for invading human bodies. Both epidemics occurred in cold dry winter seasons celebrated with major holidays, and started in regions where dietary consumption of wildlife is a fashion. Thus, if bats were the natural hosts of SARS-CoVs, cold temperature and low humidity in these times might provide conducive environmental conditions for prolonged viral survival in these regions concentrated with bats. The widespread existence of these bat-carried or -released viruses might have an easier time in breaking through human defenses when harsh winter makes human bodies more vulnerable. Once succeeding in making some initial human infections, spreading of the disease was made convenient with increased social gathering and holiday travel. These natural and social factors influenced the general progression and trajectory of the SARS epidemiology. However, some unique factors might also contribute to the origination of SARS in Wuhan. These factors are discussed in different scenarios in order to promote more research for achieving final validation.

Thermoresponsive surfaces designed for the proliferation and differentiation of human pluripotent stem cells.

Thermoresponsive surfaces enable the detachment of cells or cell sheets by decreasing the temperature of the surface when harvesting the cells. However, human pluripotent stem cells (hPSCs), such as embryonic stem cells and induced pluripotent stem cells, cannot be directly cultured on a thermoresponsive surface; hPSCs need a specific extracellular matrix to bind to the integrin receptors on their surfaces. We prepared a thermoresponsive surface by using poly(N-isopropylacrylamide-co-butylacrylate) and recombinant vitronectin to provide an optimal coating concentration for the hPSC culture. hPSCs can be cultured on the same thermoresponsive surface for 5 passages by partial detachment of the cells from the surface by decreasing the temperature for 30 min; then, the remaining hPSCs were subsequently cultured on the same dishes following the addition of new cultivation media. The detached cells, even after continual culture for five passages, showed high pluripotency, the ability to differentiate into cells derived from the 3 germ layers and the ability to undergo cardiac differentiation.

Efficient differentiation of human pluripotent stem cells into cardiomyocytes on cell sorting thermoresponsive surface.

The current differentiation process of human pluripotent stem cells (hPSCs) into cardiomyocytes to enhance the purity of hPSC-derived cardiomyocytes requires some purification processes, which are laborious processes. We developed cell sorting plates, which are prepared from coating thermoresponsive poly(N-isopropylacrylamide) and extracellular matrix proteins. After hPSCs were induced into cardiomyocytes on the thermoresponsive surface coated with laminin-521 for 15 days, the temperature of the cell culture plates was decreased to 8-9 °C to detach the cells partially from the thermoresponsive surface. The detached cells exhibited a higher cardiomyocyte marker of cTnT than the remaining cells on the thermoresponsive surface as well as the cardiomyocytes after purification using conventional cell selection. The detached cells expressed several cardiomyocyte markers, such as α-actinin, MLC2a and NKX2.5. This study suggested that the purification of hPSC-derived cardiomyocytes using cell sorting plates with the thermoresponsive surface is a promising method for the purification of hPSC-derived cardiomyocytes without conventional laborious processes.