BACKGROUND: Infections caused by Salmonella spp. remain an important public health threat especially in developing countries. In recent years, rapid emergence of antibiotics resistance has resulted in the inefficacy of available treatment options which has led to exponential increase in mortality and economic burden. The study aimed to screen Salmonella spp. for resistance genes to frequently used antibiotics and establishing the distribution of these genes across Niger State. METHODS: Ninety-eight samples comprising 72 raw meat and 26 stool samples were analyzed for the presence of Salmonella spp. Antimicrobial susceptibility of Salmonella isolates was determined by the Kirby-Bauer disc diffusion method and amplification of resistance genes namely bla(TEM), catP and gyrA were carried out using nested polymerase chain reaction (PCR) technique. RESULTS: Thirty-one (31.6%) isolates were positive for Salmonella spp. The distributions of the isolates were 22 of 31 (70.97%) in raw meat and nine of 31 (29.03%) in stool. Salmonella isolates were susceptible to ciprofloxacin (93.5%) but highly resistant to ampicillin (100%), chloramphenicol (96.8%), nalidixic acid (93.5%), tetracycline and ceftriaxone (90.3%), erythromycin (77.4%), cotrimoxazole (64.5%). High levels of bla(TEM) and catP genes and relatively low gyrA gene distributions were observed in isolates from stool and raw meat samples across the state. CONCLUSIONS: These data suggest that there is a high prevalence of ampicillin and chloramphenicol resistance by Salmonella spp. as shown by high levels of bla(TEM), gyrA and catP genes while gyrA distribution is rare across Niger State.
Hepatic fibrosis is characterized by the disruption of normal liver architecture due to proliferation of hepatic myofibroblasts, and excess of extracellular matrix (ECM) deposition. The final stage of liver diseases, cirrhosis, is common across the spectrum of chronic hepatitis such as viral hepatitis, alcoholic and non-alcoholic hepatitis, and autoimmune hepatitis. Although several molecular mechanisms involved in fibrogenesis are common in all etiologies, some of them may differ for certain aspects. A key feature of hepatic fibrosis is the activation and proliferation of hepatic stellate cells (HSCs) that become able to produce extracellular matrix ECM components. The altered ratio between ECM deposition and matrix turnover contributes to fibrogenesis with the risk of progression of liver disease. Fibrogenesis enhances an inflammatory process contributing to the activation of immune cells that reach the site of injury releasing pro-inflammatory cytokines. Moreover, other cells contribute to the activation of HSCs, for example Kupffer cells (KCs) (resident macrophages), endothelial cells and hepatocytes. In this review we summarize molecular mechanisms of hepatic fibrogenesis in the setting of the main chronic liver diseases (CLD) (alcoholic hepatitis, viral hepatitis and non-alcoholic steatohepatitis) focusing on the emerging issues involved in the onset and progression of liver damage.
BACKGROUND: Bacteriophages are a long-overlooked component of the virobiota that have the potential to shape mammalian immunity. The aim of our study was to identify a bacteriophages communities in urinary tract infections (UTIs). METHODS: We sampled the urine from 151 children having urinary tract infections, and 49 healthy controls. We decide to investigate at least one of the member of Caudovirales and Microviridae by real time PCR on urine. RESULTS: We demonstrate that bacteriophage phi V10 was more abundant in UTIs than in healthy subjects (P<0.004) and at the contrary, bacteriophage phi FL4A was more abundant in healthy subjects that in UTI samples. CONCLUSIONS: We demonstrated in UTIs an abundance of bacteriophage phi V10. Further studies will be necessary to understand how resident prokaryotic phages and eukaryotic viruses shape commensal bacterial communities.
BACKGROUND: Mannanase has been used for the hydrolysis of mannan, which is produced by many microorganisms including bacteria. The purified enzyme can be utilized in the production of high-value product such as mannooligosaccharides as prebiotics. This study aimed at purification of extracellular beta-mannanase from Proteus vulgaris using an aqueous polymer impregnated resin system. METHODS: The effect of extraction solution (potassium phosphate, sodium citrate and sodium acetate) on the stability of beta-mannanase activity was studied. The parameters which influence the purification performance such as molecular weight and concentration of PEG, concentration of salts, pH of salt, crude loading and extraction time were investigated using one-factor-at-a-time (OFAT). The effect of type and concentration of salts and pH on purification fold and yield in back extraction were also evaluated. RESULTS: beta-mannanase from Proteus vulgaris was purified using aqueous impregnated resin system with a purification fold of 10.7 and yield of 33.7% at 30% (w/w) PEG 4000 (g/mol) impregnated resins, 20% (w/w) of potassium phosphate at pH 7 with 4% (w/w) of NaCl. The back-extraction solution was 20% (w/w) potassium phosphate at pH 7. CONCLUSIONS: In conclusion, aqueous impregnated resin system offers the possibility to tailor a selective and customized purification system for beta-mannanase.
Different strategies are used for plant transformation, including electroporation, particle bombardment, polyethylene-mediated, Agrobacterium-mediated, nuclease-induced, RNA interference, and recombinase technology. Unfortunately, even after decades of developments in these transformation techniques, the regeneration potential remains troublesome in most of the crops due to their intricate genomic pattern. Further, the risk factors associated with human health and environment due to the presence of antibiotic resistance genes and foreign DNA in genetically modified (GM) crops restricts their acceptance and commercialization. These concerns seek the researcher's attention to develop new strategies and advanced tools for crop transformation. For example, the use of cisgenesis and intragenesis where the genetic material is derived from the species itself or from sexually compatible species and the engineering of existing Agrobacterium and other microbes like Rhizobium etli and Ensifer adhearens which facilitate the transfer of DNA/protein into the host plant cells, would pave the way for commercialization of GM crops in the areas where these were poorly accepted in the past. Besides, novel genome editing tools are developed, which produce crops with improved resistance to different biotic and abiotic stresses, which ultimately results in high yield. These developments have facilitated deep insights into plant biology and renovated commercial agriculture. Nonetheless, further simplification and optimization of these crop transformation strategies are essential to minimize the culture time and barriers. This review discusses the recent advancements in crop transformation and highlights several issues to be addressed for further improvement of the existing crop genome editing strategies.
BACKGROUND: Thiopurine-related hematoxicity is clinically relevant and therapy-limiting in treatment of patients with acute lymphoblastic leukemia (ALL) or inflammatory bowel disease (IBD). For clinical implementation, the Clinical Pharmacogenetics Implementation Consortium (CPIC) published peer-reviewed and evidence-based gene/drug clinical practice guidelines indicating preemptive TPMT genotype-guided thiopurine-dose individualization to mitigate drug toxicity. Recently loss-of-function germline variants in NUDT15 have been identified as additional genetic determinants of thiopurine intolerance. METHODS: We used a TaqMAMA genotyping PCR assay NUDT15-MAMAPCR real time cod. BioMole 020 for detection of c.415 C-to-T transition (rs116855232) variant of the nucleoside diphosphate-linked moiety X motif 15 (NUDT15) gene on 7500 Real-Time PCR System and CFX96 Real-Time PCR System. Subsequently we used this assay in subject with thiopurine treatment. RESULTS: Homozygotes and heterozygotes condition were tested. We reported the Delta Ct obtained from mimic homozygotes C/C (CtsC 22.31, CtaT 28.90 with Delta Ct 6.59) and T/T (CtsT 22.75, CtaC 31.01 with Delta Ct 8.26) and heterozygotes C/T conditions (CtsC 23.33, CtsT 23.72 with Delta Ct 0.38). For the clinical validation of the techniques we analyzed a population of 31 thiopurine treated pediatric patients blood samples (13 male, 18 female). All 31 samples were tested with 31/31 (100%) homozygotes (31 CC). CONCLUSIONS: The CFX96 Real-Time PCR System is a suitable instrument to use in conjunction with the NUDT15-MAMAPCR real time to generate predictive information about genotyping assay of rs116855232, C415T polymorphism in children with thiopurine treatment.
BACKGROUND: Norovirus (NoV) infection is a major cause of non-bacterial pediatric gastroenteritis throughout the world. The availability of molecular methods (including molecular typing) has led to the frequent detection of NoVs in recent years. The aim of this paper was to review pediatric NoV infection in Turin, Piedmont, Italy. METHODS: A total of 137 fecal specimens previously screened for rotavirus and adenovirus were tested for NoV virus. RESULTS: NoV was detected in a total of 62/137 patients (45.26%): of these, 49 (79.03%) presented the genotype II virus, 6 (9.68%) the genotype I and in 7 patients (11.29%) the presence of viruses both of the GI and of the GII was found. In our study, the NoV was detected as the sole etiological agent responsible for gastroenteritis in 28.36% of patients who performed viral research also for rotavirus and adenovirus. CONCLUSIONS: The evident importance of the NoV on an epidemiological level in our territory therefore suggests the idea that, if the data were confirmed over the long term, the search for this pathogen could have a role in the hospital routine, compatible with a cost-benefit analysis to be carried out regarding the use of RT-PCR, the most sensitive and specific method currently available for the diagnosis of norovirosis.
BACKGROUND: Microparticles (MPs) are phospholipid vesicles shed by different cell types during activation or apoptosis, that mediate intercellular communications. Monocyte-derived MPs up-regulate the synthesis of proinflammatoiy mediators in lung epithelial cells, but their direct effects on human alveolar macrophages (AM) have been never evaluated. Pemxisome Proliferator-activated receptor-gamma (PPAR gamma) activation usually exerts anti-inflammatory effects, PPAR gamma agonists showing beneficial effects in experimental models of asthma. In this study we aimed at assessing the ability of monocyte-derived MPs to stimulate AM isolated from patients with sarcoidosis, and the possible modulation by PPAR gamma. METHODS: MPs were generated from supernatants of A23187-stimulated human monocytes. AM were challenged by MPs or PMA (used as standard stimulus), in the absence or presence of PPAR gamma agonists and antagonists, and evaluated for superoxide anion production, cytokine release, nuclear factor (NF)-kappa B activation and PPAR gamma expression. RESULTS: Monocyte-derived MPs induce, in a concentration-dependent manner, oxy-radical production, cytokine release and NF-kappa KB activation in AM, with lower effects than PMA. PPAR gamma agonists inhibit MPs-induced stimulation, these effects being reversed by the specific antagonist, GW9662. MPs also induce PPAR gamma protein expression, as do selective agonists. CONCLUSIONS: In human AM, MPs induce relevant pro-inflammatory effects, that are reduced by PPAR gamma agonists, but also enhance PPAR gamma expression, so providing a possible auto-regulatory anti-inflammatory loop.
BACKGROUND: Since no routine tests for the fusariosis diagnosis are currently available and DNA-based techniques for detection are not yet fully standardized or commercially available, the aim of this study was to develop new procedures to perform a rapid fungal identification vital to patient management. METHODS: Polymerase chain reaction (PCR) was set up in a volume of 20 mu L, containing 100 ng of DNA (20 ng/mu L) and 15 mu L of amplification mix Fusarium solani PCR real time. RESULTS: Efficiency and sensitivity, variability, specificity and dynamic range were tested. The reproducibility was expressed as the coefficient of variation (CV) in the log10 values of the concentration. Quantification of Fusarium solani was highly reproducible for as few as 10(2) copies. The RT-PCR assay was able to quantify Fusarium solani from 10(9) to 10(2) copies/reaction. CONCLUSIONS: The performance of our real time PCR assay using samples from culture was excellent, with 100% sensitivity and no cross-reactivity demonstrated with the tested species of other microbes. Real time PCR offers significant improvements to microbial load quantitation because of its wide dynamic range, which can accommodate at least eight log10 copies of nucleic acid template. The RT-qPCR TaqMan assay described herein can be utilized to provide an objective result either as a separate test or as a complement to microscopy.
BACKGROUND: Mild traumatic brain injury (mTBI) represents one of the main causes of emergency department (ED) admission. Microvesicles (MVs) have been shown to play an important role in cell-to-cell communication. However, their role in mTBI needs to be clarified. METHODS: Patients admitted to the ED for mTBI, with or without minor trauma of the limbs, were enrolled. Patients with isolated minor trauma of the limbs served as control group. Five healthy volunteers were also enrolled. Blood sample was collected within 8 hours from admission and plasmatic MVs were subsequently isolated and quantified. Through flow cytometry MVs were further characterized on a subgroup of patients and controls. A 30-day follow-up phone call evaluated the presence of post-traumatic sequelae. RESULTS: One hundred and fifteen mTBI and 40 control patients were enrolled between July 2014 and March 2015. Plasma MVs size and concentration were significantly higher (P=0.0011 and P<0.0001, respectively) in mTBI patients compared to both controls and healthy volunteers. No difference was observed in terms of MVs concentration and size neither according to age, sex, anticoagulant therapy nor presence of post-traumatic sequelae. At MVs characterization, (FAS-Ligand expression was significantly higher in mTBI patients compared to controls (P=0.035). CONCLUSIONS: Both plasmatic MVs size and concentration are significantly higher in patients admitted to the ED for mTBI, compared to controls and healthy subjects.
BACKGROUND: Nowadays, great attention has been directed to novel gene editing platforms including CRISPR/Cas9 systems. It appears that carbon dots (CDs) might be considered as potential candidates for gene delivery. METHODS: In the present study, we sought to find an efficient non-viral nanocarrier system to transfer CRISPR/Cas9 plasmid into A549 cell line. The characterization of CDs was performed using transmission electron microscopy, fluorescence emission spectra and zeta (zeta) potential measurement. The delivery potential and biocompatibility of CDs were evaluated using cell uptake (bioimaging) and cell viability assay, respectively. RESULTS: The CDs had positive charge (+32mV) with spherical shape. The cationic CDs could condense the CRISPR plasmid (pCRISPR) efficiently. Significant viability of the cells following the treatment with CDs demonstrated low toxicity while the CDs could deliver the system into the cells effectively. CONCLUSIONS: According to our results, cationic CDs have shown potential to act as gene carriers for CRISPR/Cas9 system.
BACKGROUND: Diallyl disulfide (DADS), a sulfuric compound derived from garlic, exerts various biological effects such as anticancer, anti-angiogenic and anti-inflammatory activities. However, the mechanisms of action underlying this compound's anticancer activity have not been fully elucidated. The aim of this study was to identify the mechanism by which AMP-activated protein kinase alpha1 (AMPK alpha 1) contributes to the anti-tumor effects of DADS. METHODS: MGC-803 cells treated with 0, 10, 20, or 40 mg/L of DADS for 48 hours were examined for glucose and lactic acid concentrations, cell viability and apoptosis using colorimetric methods, a cell counting kit (CCK8) and flow cytometry, respectively. The protein expression levels of AMPK alpha 1 and lactate dehydrogenase A (LDHA) in the cells were detected with western blotting. The mRNA expression of AMPK alpha 1 was measured with quantitative real-time PCR (qRT-PCR), and shRNA targeting AMPK alpha 1 as well as a scrambled shRNA were transfected into MGC-803 cells using Lipofectamine 2000. RESULTS: Inhibition of aerobic glycolysis was observed in DADS-treated MGC-803 cells as indicated by increases in the glucose concentration in the medium, decreases of lactate production in the medium and down-regulation of AMPK alpha 1 and LDHA expression. Meanwhile, DADS inhibited proliferation and induced apoptosis in a concentration-dependent manner. Furthermore, AMPK alpha 1 was identified as a target of DADS. AMPK alpha 1 is overexpressed in many cancers, and down-regulation of AMPK alpha 1 inhibited proliferation and induced apoptosis of MGC-803 human gastric cancer cells in vitro by suppressing aerobic glycolysis induced by DADS. CONCLUSIONS: We demonstrated that DADS could induce apoptosis, inhibit proliferation and suppress aerobic glycolysis by down-regulating AMPK alpha 1.
Helicobacter pylori (H. pylori) infection is one of the most common diseases in the world. According to epidemiological data, the infection rate of the population can vary from 30% to 90% depending on the country. This infection is associated with the development of chronic gastritis, peptic ulcer disease and malignant neoplasms of the stomach (gastric adenocarcinoma and mucosa-associated lymphoid tissue - lymphoma). H. pylori is a kind of "pioneer" among bacteria: it is not only the first bacterium with proven carcinogenicity, but also one of the first bacteria to have its genome decoded. Modern science cannot be imagined without the use of molecular genetic research to study microorganisms: decoding the genomes of known pathogens, studying the pathogenesis of the diseases based on pathogenicity genes, monitoring the spread of antibiotic resistance, tracking the circulation of various genotypes for epidemiological labeling of strains, creating diagnostic tests for accelerated diagnosis of infection, and developing new diagnostic and preventive approaches. The purpose of this short review is to analyze modern molecular genetic methods for detecting H. pylori. The use of molecular methods significantly expanded our ability to study H. pylori as the causative agent of a disease, while not abolishing the use of the classical culture method, and are an excellent tool to investigate previously unknown mechanisms of the pathogenesis of H. pylori infection, to conduct rapid diagnosis and determine the strategy for eradication therapy.
BACKGROUND: Pre-eclampsia is a disorder marked by hypertension during pregnancy that is a leading cause of maternal and infant morbidity, mortality, and premature births worldwide. Pre-eclampsia is thought to result from a poor placental perfusion of unclear causes. Gene expression profiles of placenta-associated genes have been shown to be altered in patients with pre-eclampsia. but the actual regulators remain unknown. We aimed to identify and analyze key regulatory genes associated with pre-eclampsia. METHODS: In this paper, we analyzed the gene expression profiles of placentas of women with first-trimester pre-eclampsia to identify key regulators; in addition, we performed protein-protein interaction, gene ontology (GO) enrichment, and pathway analyses. RESULTS: After applying log fold-change statistics, we found 231 differentially expressed genes (DEGs) between normal and pre-eclampsia placentas. We confirmed through downstream analyses that these genes are associated with CYP-mediated steroid metabolism and hydroxylation in pregnancy, with glucuronidation and hyperbilirubinemia and with other biological pathways. CONCLUSIONS: The identified DEGs associated with pre-eclampsia may be targeted in studies to clarify the pathogenesis of this condition.
BACKGROUND: The emergency of polymyxin resistance gene mcr-1 located on plasmids has aroused great concern about the lack of medicine for bacterial infection. METHODS: In this study, a strain of Escherichia coli harboring mcr-1 was recovered from mink liver. The drug-resistant genes were determined by PCR. Identification of bacteria was determined by combination of biology phenotype, chemical tests, 16SrRNA, minimum inhibition concentration and mass spectrometry. Complete genome sequence was done with the method of Nanopore. The plasmid map was drawn with Snapgene Viewer software. RESULTS: Results of PCR and complete genome sequencing of nrcr-1 were all positive. Results showed the bacteria were Gram negative. lactose test positive, indole test positive, MR test positive and VP test Negative. The results of mass spectrometry showed that DH5 alpha was the reference strain, and the MLST Test showed the strain of Escherichia coli was ST140.The complete genome sequence showed that the whole length was 5,316,854bp and contained three contigs, one of which was chromosome and the other two plasmids. CONCLUSIONS: Drug resistant gene gryA was located on chromosome while mcr-1 and sul antibiotic genes were located on plasmid 1 and Bla(CTX-M-1) was located on plasmid 2. To our knowledge, this is the first report of a polymyxin resistance plasmid harboring Sul2.
Occult hepatitis C virus infection (OCI) is defined by the presence of detectable HCV-RNA in liver tissue but not in serum without detectable anti-HCV antibodies (seronegative or primary OCI) or with detectable anti-HCV antibodies (seropositive or secondary OCI). The latter is considered a persistence of virus activity after appropriate antiviral therapy, whilst the former may be related to a mutation which prevents virus encapsidation, and the immune system from mounting an appropriate response. Seronegative OCI has been widely investigated as a possible cause of liver damage in patients with hepatitis, cirrhosis and in liver transplant recipients. OCI has been searched for in cryptogenic liver disease, alcoholic and non-alcoholic fatty liver disease, hepatitis B virus infection and hepatocellular carcinoma, as concomitant cause of liver damage. Liver biopsy is currently the gold standard for diagnosis of OCI. Non-invasive tests, such as search for HCV-RNA in peripheral blood mononuclear cells, can also reach acceptable diagnostic accuracy. Response to antiviral therapy has been reported. However, more studies are needed to determine whether treatment can modify morbidity and/or mortality associated to liver disease. OCI has also been investigated in special populations, like kidney transplant recipients or human immunodeficiency virus-infected patients, as worsening factor of the underlying disease. Lastly, some studies have been conducted on healthy populations, such as blood donors, with consequent concern arising from possible asymptomatic OCI infectivity. Few observational studies with a long-term follow-up have been conducted, with discordant results. Additional and larger studies are needed to clarify the natural course of OCI and to assess its clinical implications. In this review we discuss these aspects of OCI.
BACKGROUND: Breast cancer (BC) is one of the most common types of women malignancy. Multi-epitope vaccines are new hopes for treatment of this cancer. MUC-1 is a tumor associated antigen that focused for multi-epitope vaccine development in case of BC. METHODS: Here, primary data from a computation analysis of this glycoprotein to find potential MHC-I, MHC-II, CTL and B-cell epitopes are described using immunoinformatics tools. RESULTS: According to the results, 1156VPGWGIALL984 corresponding to HLA-B0702 and HLA-A0101 alleles for MHC-I epitopes, 1209YPTYHTHGR1118 corresponding to DRB1*13 and DQB1*06 alleles for MHC-II epitops, 1122NQYKTEAAS45 for CTL epitopes and 1204HPMSEYPTYHTHGRYV896 for B-cell epitopes are the peptides with the best binding affinity. CONCLUSIONS: These data may be useful for further multi-epitope vaccine development.
INTRODUCTION: The search for non-invasive tools aiming to assess liver fibrosis and inflammation, and able to replace liver biopsy, remains one of the most important unmet need in clinical practice. Although cytokeratin 18-Asp396 (CK18-Asp396) apoptotic fragment has been considered an important marker of hepatitis progression, until now, conflicting results have been reported. Therefore, we performed a meta-analysis to evaluate the diagnostic accuracy of CK18-Asp396 for the detection of fibrosis and inflammation in patients with chronic hepatitis C (CHC) and chronic hepatitis B (CHB) infection.EVIDENCE ACQUISITION: Through PubMed and Scopus databases, we identified published papers on the evaluation of the diagnostic performance of CK18-Asp396 for the discrimination of patients with significant fibrosis and inflammation. Statistical analysis was performed with MedCalc Software.EVIDENCE SYNTHESIS: A total of 11 studies (425 patients with CHC and 1012 patients with CHB infection) were included in the meta-analysis. The median cut-off value of CK18-Asp396 marker for the identification of significant fibrosis was higher compared to the median cut-off value for the discrimination of significant inflammation (294 U/L vs. 234 U/L, P=0.05). The weighted summary area under the curve (sAUC) of CK18-Asp396 for the detection of significant fibrosis and inflammation was 0.75 (95% confidence interval [CI]=0.66-0.83) and 0.75 (95% CI=0.70-0.79), respectively. No difference was observed between the diagnostic performance of CK18-Asp396 in identifying significant fibrosis and significant inflammation.CONCLUSIONS: The measurement of serum CK18-Asp396 showed a moderate diagnostic accuracy for the detection of both significant fibrosis and significant inflammation in patients with chronic viral hepatitis. Possibly, the combination of CK18-Asp396 with other biomarkers of disease severity may improve its diagnostic performance.
BACKGROUND: Sepsis is the most common cause of mortality in intensive care units. The activation of toll-like receptor 4 (TLR4) and its recognition by myeloid differentiation 2 (MD-2) amplify a cascade of cytokinin production responsible for the inflammation in sepsis.METHODS: We designed a drug discovery study screening for sepsis treatments that included network analysis and prediction of protein-protein interactions (PPIs), molecular docking and possible toxicity evaluation. We identified the phytoconstituents of Xuebijing (XBJ) in the literature and tabulated them to construct a network analysis and identify all the bioactive agents according to their organic class.RESULTS: Our molecular docking analysis showed strong binding energies for cryptotanshinone and tanshinone IIA (docking scores for MD-2 of -9.3 and -9.2 kcal/mol, respectively). We identified MD-2 as a target of the potent bioactive component cryptotanshinone confirming a possible inhibitory effect against the cytokine response causing sepsis.CONCLUSIONS: Our findings suggest that the phytoconstituent cryptotanshinone may inhibit the inflammatory cascade in sepsis and should be studied as a candidate treatment against sepsis-like diseases.
Scaling up of micro bioreactors is not always an economical or practicable process. Though, some extra cases of successful trends of micro bioreactors industrialization have been reported and shown many developments until the present time. It has not been feasible yet to get a generalized formula for scale up; One that is gotten from the specifications of a certain system, so that it would account for any specific system's specifications under arbitrary operating parameters values and various circumstances. Being aware of the selectivity, outstanding developments, the uprising techniques and new systems introduced in the present decade, the need for a complete research of the evolutionary approaches and their prerequisites, representation of their usefulnesses, their drawbacks and limitations seems essential. These urgent needs will be addressed as a review here; So that there will be a prologue in hand for later novel engineering ideas, and the limitations in the field of reaching to industrial micro bioreactors are removed.
