Stem cell induced inflammatory hypertrophy of the cauda equina.

Stem cell therapy can present clinicians with challenging clinical scenarios, as access to such treatments outpaces the research into their efficacy and safety due to the burgeoning trend of international travel to acquire stem cell therapy, or "stem cell tourism." Treatment of neurologic conditions remains an enticing potential application of stem cell therapy, often administered intrathecally. In response to such therapy, multiple adverse events have been described in the literature, including neoplasms, demyelinating disease, and seizures, among others. We present a case of symptomatic inflammatory cauda equina nerve root hypertrophy due to intrathecal stem cell infusion, representing a rare but significant complication.

Challenges in Treating Statin-Associated Necrotizing Myopathy.

Myalgia and mild elevation in muscle enzymes are common side effects of statin therapy. While these symptoms are generally self-limited, in rare cases, statin use is associated with an immune-mediated necrotizing myopathy caused by development of autoantibodies against HMG-CoA reductase. The primary presenting symptom of this condition is progressive symmetric proximal weakness that does not abate or worsens even after cessation of statin therapy and is associated with markedly elevated creatine kinase (CK) levels. To date, no randomized controlled trials have been conducted to identify the most effective treatment for statin-associated autoimmune myopathy. Treatment recommendations involve a combination of steroids and immunosuppressive drugs. This single-center case series highlights the clinicopathologic features diagnostic for statin-associated autoimmune myopathy as well as treatment challenges for the patient population. The series highlights a range of potential presentations, from mildly symptomatic despite highly elevated CK, to severe muscle weakness including dysphagia. Multiple patients required several immunosuppressant medications as well as intravenous immunoglobulin (IVIG) to achieve disease control. In this case series, marked improvement was noted in several diabetic patients with IVIG.

Disseminated Herpes Simplex Virus in an Immunocompetent Patient Without Presence of Epidermal or Mucosal Lesions.

ABSTRACT: Herpes simplex virus (HSV) is a disease usually characterized by lesions within the epidermis or mucosa of children and adults. However, this infection can also cause complications to many systems of the body, including the peripheral and central nervous system, respiratory system, and hepatobiliary system. In this case, we present a 43-year-old man with a history of substance abuse, who presented with fever, cough, and headache, and within days, progressed into fulminant hepatitis and hypoxic failure. Bacterial and fungal cultures were negative, as well as the workup for human immunodeficiency virus. However, the presence of HSV was detected in a bronchial lavage culture after the patients had expired. This result, along with the findings at autopsy, including viral cytopathic effect in the lung and liver, which were confirmed with immunohistochemical stains for HSV, strongly suggest that the cause of death is from disseminated herpes virus infection with hepatitis and viral pneumonitis. This disseminated infection occurred in an immunocompetent host without any evidence of mucocutaneous lesions.

Enzymatic decolorization of melanin by lignin peroxidase from Phanerochaete chrysosporium.

Skin darkening results as a consequence of the accumulation of skin pigment melanin. To combat this, the amplitude of skin lightening agents are commercially available, most of which inhibit melanin synthesis. Decolorization of melanin is an alternative method of skin lightening. In this study, we show that lignin peroxidase (LiP), an extracellular enzyme purified from Phanerochaete chrysosporium NK-1 isolated from a forest soil can effectively degrade and decolorize melanin in vitro. Decolorization conditions including pH, temperature, incubation time, enzyme concentration, and mediator addition were investigated to optimize the reaction conditions. The results indicate that pH 3, 40 °C, 15 IU/ml, and 10 h incubation were the optimal conditions for the decolorization of the melanin. The use of the mediator, veratryl alcohol was also found effective to enhance the efficacy of the melanin decolonization, with up to 92% decolorization. The scanning electron microscopy results showed void spaces on the treated melanin granules as compared to the untreated sample, indicating the degradation of melanin. Changes in the fingerprint region of the melanin were observed. Between wavenumbers 1500-500 cm-1, for example, the presence of new peaks in the treated melanin at 1513, 1464, and 1139 cm-1 CH2, CH3 bend and C-O-C stretch represented structural changes. A new peak at 2144 cm-1 (alkynyl C≡C stretch) was also detected in the decolorized melanin. The cytotoxicity study has shown that the treated melanin and LiP have low cytotoxic effects; however, the mediator of veratryl alcohol could result in high mortality which suggests that its use should be meticulously tested in formulating health and skincare products. The findings of the study suggest that LiP produced by Phanerochaete chrysosporium has the potential to be used in the medical and cosmetic industries, particularly for the development of biobased cosmetic whitening agents.

Structural vaccinology approach to investigate the virulent and secretory proteins of Bacillus anthracis for devising anthrax next-generation vaccine.

Communicated by Ramaswamy H. Sarma.

Lignin peroxidase isoenzyme: a novel approach to biodegrade the toxic synthetic polymer waste.

Fungal metabolites are playing an immense role in developing various sustainable waste treatment processes. The present study aimed at production and characterization of fungal lignin peroxidase (EC 1.11.1.14) with a potential to degrade Polyvinyl Chloride. Optimization studies revealed that the maximum enzyme production occurred at a temperature 25°C, pH 5 in the 4th week of the incubation period with fungal strain. Enzyme assay was performed to find out the dominating enzyme in the culture broth. The molecular weight of the enzyme was found to be 46 kDa. Partially purified lignin peroxidase from Phanerocheate chrysosporium was used for the degradation of PVC films. A significant reduction in the weight of PVC film was observed (31%) in shake flask experiment. FTIR spectra of the enzyme-treated plastic film revealed structural changes in the chemical composition, indicating a specific peak at 2943 cm-1 that corresponded to alkenyl C-H stretch. Moreover, deterioration on the surface of PVC films was confirmed by Scanning Electron Microscopy tracked through activity assay for the lignin peroxidase. Extracellular lignin peroxidases from P. chrysosporium play a significant role in the degradation of complex polymeric compounds like PVC.

Exploratory algorithm to devise multi-epitope subunit vaccine by investigating Leishmania donovani membrane proteins.

Visceral leishmaniasis (VL) is a deadly parasitic infection which affects poorest to poor population living in the endemic countries. Increasing resistant to existing drugs, disease burden and a significant number of deaths, necessitates the need for an effective vaccine to prevent the VL infection. This study employed a combinatorial approach to develop a multi-epitope subunit vaccine by exploiting Leishmania donovani membrane proteins. Cytotoxic T- and helper T-lymphocyte binding epitopes along with suitable adjuvant and linkers were joined together in a sequential manner to design the subunit vaccine. The occurrence of B-cell and IFN-γ inducing epitopes approves the ability of subunit vaccine to develop humoral and cell-mediated immune response. Physiochemical parameters of vaccine protein were also assessed followed by homology modeling, model refinement and validation. Moreover, disulfide engineering was performed for the increasing stability of the designed vaccine and molecular dynamics simulation was performed for the comparative stability purposes and to conform the geometric conformations. Further, molecular docking and molecular dynamics simulation study of a mutated and non-mutated subunit vaccine against TLR-4 immune receptor were performed and respective complex stability was determined. In silico cloning ensures the expression of designed vaccine in pET28a(+) expression vector. This study offers a cost-effective and time-saving way to design a novel immunogenic vaccine that could be used to prevent VL infection. Communicated by Ramaswamy H. Sarma.

Examination of antigenic proteins of Trypanosoma cruzi to fabricate an epitope-based subunit vaccine by exploiting epitope mapping mechanism.

Chagas disease is a protozoan parasitic disease caused by Trypanosoma cruzi. This injurious disease spread by the circulation of the blood sucking triatomine insects and transmitted to humans. Chagas disease is endemic in Latin America and also known as American trypanosomasis. Currently, 7 million people are infected by T. cruzi infection and about 22,000 death cases were reported per year throughout the Americas. Various immunization approaches against T. cruzi infection have been examined and some of the developed vaccine showed efficacy in animal models but there is no effective and safe vaccines for humans have been developed yet. Since, the drug resistance is increasing day by day because the developed drug (nifurtimox and benznidazole) to control T. cruzi infection, failed to activate a prodrug and still no drug and vaccine have been established. To control the infection of chagas disease, here in this study we use immunoinformatics method to design multi-epitope subunit vaccine against T. cruzi infection. Moreover, on the basis of immunogenicity B and T cell epitopes were evaluated. The allergenicity, antigenicity was predicted to ensure the safety of vaccine constructs whereas, the physiochemical property showing the stable nature of final vaccine model. Further, molecular docking was performed to optimize the interaction between TLR-2 and TLR-4 (receptor) and vaccine model (ligand) complex. Molecular dynamics simulation was performed to evaluate the energy minimization; RMSD and RMSF plot which confirm the stability of TLR-2 and TLR-4 (receptor) present on immune cells and vaccine model (ligand) complex. This study needed the experimental validation for the safety and immunogenic behavior of designed vaccine protein and it may be helpful in future to control T. cruzi infection.

Scrutinizing Mycobacterium tuberculosis membrane and secretory proteins to formulate multiepitope subunit vaccine against pulmonary tuberculosis by utilizing immunoinformatic approaches.

Tuberculosis is a menacing disease caused eminently to the people inhabiting the tropical and sub-tropical nations. A holistic approach is required to generate T and B memory cells to effectuate a long-term exemption from the pulmonary tuberculosis. In this study, immunoinformatic approaches were used to design a multi-epitope-based subunit vaccine for pulmonary tuberculosis which may improve human immune system. The various B-cell, TH cell and TC cell binding epitopes were predicted for selected 2 membrane and 12 secretory proteins of Mycobacterium tuberculosis. The final vaccine construct was assembled by merging the predicted epitope sequences and an adjuvant at the N-terminal of the construct. Furthermore, the physiochemical characterization was done to check the molecular weight, aliphatic index, theoretical PI, hydropathicity and thermostable nature of the designed vaccine. The construct was a potential antigen while wasn't allergenic in nature. Tertiary modeling was performed, by filtering them a refined model was chosen and was docked with TLR-4 (immune receptor). Molecular docking and dynamic simulation was performed and the microscopic interaction between the vaccine construct (ligand) and TLR-4 receptor complex was verified. In silico cloning was used to fortify the expression and translation efficiency of the vaccine within an expression vector.

Conglomeration of novel Culex quinquefasciatus salivary proteins to contrive multi-epitope subunit vaccine against infections caused by blood imbibing transmitter.

The southern house vector, Culex quinquefasciatus is the paramount cause of Japanese encephalitis, West Nile fever and Lymphatic Filariasis, which is globally affecting the worldwide population. Many attempts were made by researchers with different perceptions to discover regimen against these aforementioned ailments but the output was not that effectual. Consequently, there is an imminent need to develop very effective and potential treatment against these perilous diseases. Employing immunoinformatic approaches, we have designed the multi-epitope subunit vaccine by exploring salivary proteins of Culex quinquefasciatus, which possess both antigenic and potent immunogenic behaviour. The immunogenic epitopes from the immune cells (B-cell, CTL, and HTL) were predicted and linked together with the help of linkers. Apart from this, at the N-terminal of the construct, an adjuvant was added in order to enhance the immunogenicity of the vaccine. The physiological parameters, antigenicity and allergenicity were also evaluated for the designed vaccine construct. Molecular docking between ligand (vaccine construct) and TLR-4 receptor was performed. Molecular dynamics simulation of the docked complex was performed to identify the stability, patterns, macromolecules interactions and their behaviour. Finally, to ensure the translation and gene expression efficiency of designed construct, insilico restriction cloning was executed into suitable expression vector pET28a.

Excavating chikungunya genome to design B and T cell multi-epitope subunit vaccine using comprehensive immunoinformatics approach to control chikungunya infection.

Chikungunya infection has been a cause of countless deaths worldwide. Due to lack of permanent treatment and prevention of this disease, the mortality rate remains very high. Therefore, we followed an immunoinformatics approach for the development of multi-epitope subunit vaccine which is able to elucidate humoral, cell-mediated and innate immune responses inside the host body. Both structural and non-structural proteins of chikungunya virus were utilized for prediction of B-cell and T-cell binding epitopes along with interferon-γ (IFN-γ) inducing epitopes. The vaccine construct is composed of ß-defensin as an adjuvant at the N-terminal followed by Cytotoxic T-Lymphocytes (CTL) and Helper T-Lymphocyte (HTL) epitopes. The same vaccine construct was also utilized for the prediction of B-cell binding epitopes and IFN-γ inducing epitopes. This was followed by the 3D model generation, refinement and validation of the vaccine construct. Later on, the interaction of modeled vaccine with the innate immune receptor (TLR-3) was explored by performing molecular docking and molecular dynamics simulation studies. Also to check the efficiency of expression of this vaccine construct in an expression vector, in silico cloning was performed at the final stage of vaccine development. Further, designed multi-epitope subunit vaccine necessitates experimental and clinical investigation to develop as an immunogenic vaccine candidate.

Exploring dengue genome to construct a multi-epitope based subunit vaccine by utilizing immunoinformatics approach to battle against dengue infection.

Dengue is considered as a major health issue which causes a number of deaths worldwide each year; tropical countries are majorly affected by dengue outbreaks. It is considered as life threatening issue because, since many decades not a single effective approach for treatment and prevention of dengue has been developed. Therefore, to find new preventive measure, we used immunoinformatics approaches to develop a multi-epitope based subunit vaccine for dengue which can generate various immune responses inside the host. Different B-cell, TC cell, and TH cell binding epitopes were predicted for structural and non-structural proteins of dengue virus. Final vaccine constructs consisting of TC and TH cell epitopes and an adjuvant (ß-defensin) at N-terminal of the construct. Presence of B-cell and IFN-γ inducing epitopes confirms the humoral and cell mediated immune response developed by designed vaccine. Designed vaccine was not found allergic and was potentially antigenic in nature. Modeling of tertiary structure and the refined model was used for molecular docking with TLR-3 (immune receptor). Molecular docking and dynamics simulation confirms the microscopic interactions between ligand and receptor. In silico cloning approach was used to ensure the expression and translation efficiency of vaccine within an expression vector.

Exploring Leishmania secretory proteins to design B and T cell multi-epitope subunit vaccine using immunoinformatics approach.

Visceral leishmaniasis (VL) is a fatal form of leishmaniasis which affects 70 countries, worldwide. Increasing drug resistance, HIV co-infection, and poor health system require operative vaccination strategy to control the VL transmission dynamics. Therefore, a holistic approach is needed to generate T and B memory cells to mediate long-term immunity against VL infection. Consequently, immunoinformatics approach was applied to design Leishmania secretory protein based multi-epitope subunit vaccine construct consisting of B and T cell epitopes. Further, the physiochemical characterization was performed to check the aliphatic index, theoretical PI, molecular weight, and thermostable nature of vaccine construct. The allergenicity and antigenicity were also predicted to ensure the safety and immunogenic behavior of final vaccine construct. Moreover, homology modeling, followed by molecular docking and molecular dynamics simulation study was also performed to evaluate the binding affinity and stability of receptor (TLR-4) and ligand (vaccine protein) complex. This study warrants the experimental validation to ensure the immunogenicity and safety profile of presented vaccine construct which may be further helpful to control VL infection.

Polymeric pollutant biodegradation through microbial oxidoreductase: A better strategy to safe environment.

The detoxification of xenobiotic organic compounds by various microorganisms through oxidative coupling is facilitated with oxidoreductases. With the help of energy yielding biochemical reactions, these microbes extract energy for their metabolic pathway. They promote the transfer of electrons from a reduced organic substrate to another chemical compound. During such oxidation-reduction reactions, the toxic polymeric substance is finally oxidized into harmless compounds. Enzymatic bioremediation of toxic organic pollutant is a very effective strategy in complex environmental conditions. Oxidoreductases enzymes have a significant potential for the bioremediation of the xenobiotic compounds. Various electron donor complex polymeric substrates containing Phenol and aromatic amines are oxidized by peroxidase in the presence of H2O2 while O2 in the case of dioxygenase. This review attempts to present relevant information on the peroxidases and dioxygenase from various microbial isolates involved in the biodegradation of a wide range of pollutants.

Plasmodium falciparum apicoplast and its transcriptional regulation through calcium signaling.

Malaria has been present since ancient time and remains a major global health problem in developing countries. Plasmodium falciparum belongs to the phylum Apicomplexan, largely contain disease-causing parasites and characterized by the presence of apicoplast. It is a very essential organelle of P. falciparum responsible for the synthesis of key molecules required for the growth of the parasite. Indispensable nature of apicoplast makes it a potential drug target. Calcium signaling is important in the establishment of malaria parasite inside the host. It has been involved in invasion and egress of merozoites during the asexual life cycle of the parasite. Calcium signaling also regulates apicoplast metabolism. Therefore, in this review, we will focus on the role of apicoplast in malaria biology and its metabolic regulation through Ca++ signaling.

Bacterial succession and degradative changes by biofilm on plastic medium for wastewater treatment.

Biofilms contain a diverse range of microorganisms and their varying extracellular polysaccharides. The present study has revealed biofilm succession associated with degradative effects on plastic (polypropylene) and contaminants in sludge. The wet weight of biofilm significantly (p < 0.05) increased; from 0.23 ± 0.01 to 0.44 ± 0.01 g. Similarly, the dry weight of the biofilm increased from 0.02 to 0.05 g. Significant reduction in pathogens (E. coli and feacal coliforms) by MPN technique (>80%) and in chemical parameters (decrease in COD, BOD5 of 73.32 and 69.94%) representing diminution of organic pollutants. Energy dispersive X-ray spectroscopy (EDS) of plastic revealed carbon and oxygen contents, further surface analysis of plastic by scanning electron microscopy (SEM) revealed emergence of profound bacterial growth on the surface. Fourier transform infrared (FTIR) spectroscopy conforms its biotransformation under aerobic conditions after 8 weeks. New peaks developed at the region 1050 and 969 cm(-1) indicating CO and CC bond formation. Thus plastic with 6 weeks old aerobic biofilm (free of pathogens, max. weight, and OD, efficient COD & BOD removal ability) is suggested to be maintained in fixed biofilm reactors for wastewater treatment.

Monitoring of growth and physiological activities of biofilm during succession on polystyrene from activated sludge under aerobic and anaerobic conditions.

The present research work monitored the successive biofilm development and its catabolic role in the degradation of polystyrene (PS). PS material was artificially colonized with biofilm by incubating it with activated sludge under aerobic and anaerobic conditions. Biofilm formation was monitored by gravimetric weight analysis, spectrophotometric absorbance technique, heterotrophic plate count, and scanning electron microscopy under aerobic and anaerobic conditions. The wet weight (1.59 and 1.17 g) and dry weight (0.41 and 0.08 g) of a biofilm showed a significant constant increase under aerobic and anaerobic conditions, respectively, from first till 9 weeks of incubation. Plate count of the selected bacteria (Escherichia coli, Salmonella typhimurium, Shigella dysenteriae, Pseudomonas aeruginosa) considerably declined (90-99 %) in the biofilm after seventh and fifth weeks of incubation under aerobic and anaerobic conditions, respectively, indicating a positive shift from pathogenic to beneficial microbial community. While most probable number index of fecal coliforms and E. coli in the sludge showed more reduction (98 and 99 %) under aerobic as compare to anaerobic conditions (86 and 91 %) after 9 weeks of biofilm formation on PS cubes. Correspondingly, the decreasing levels of chemical oxygen demand and biochemical oxygen demand (up to 73 %) showed signs of sludge digestion. Scanning electron microscope coupled with energy dispersive X-ray spectroscope revealed nature of PS media containing high carbon content. However, biofilm development proved to be involved in the biochemical transformation of the PS medium as indicated by Fourier transform infrared spectroscopy.