Heterozygous Truncating Variants in POMP Escape Nonsense-Mediated Decay and Cause a Unique Immune Dysregulatory Syndrome.

The proteasome processes proteins to facilitate immune recognition and host defense. When inherently defective, it can lead to aberrant immunity resulting in a dysregulated response that can cause autoimmunity and/or autoinflammation. Biallelic or digenic loss-of-function variants in some of the proteasome subunits have been described as causing a primary immunodeficiency disease that manifests as a severe dysregulatory syndrome: chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE). Proteasome maturation protein (POMP) is a chaperone for proteasome assembly and is critical for the incorporation of catalytic subunits into the proteasome. Here, we characterize and describe POMP-related autoinflammation and immune dysregulation disease (PRAID) discovered in two unrelated individuals with a unique constellation of early-onset combined immunodeficiency, inflammatory neutrophilic dermatosis, and autoimmunity. We also begin to delineate a complex genetic mechanism whereby de novo heterozygous frameshift variants in the penultimate exon of POMP escape nonsense-mediated mRNA decay (NMD) and result in a truncated protein that perturbs proteasome assembly by a dominant-negative mechanism. To our knowledge, this mechanism has not been reported in any primary immunodeficiencies, autoinflammatory syndromes, or autoimmune diseases. Here, we define a unique hypo- and hyper-immune phenotype and report an immune dysregulation syndrome caused by frameshift mutations that escape NMD.

Protective effect of proton pump inhibitors and potassium competitive acid blockers against post-gastric endoscopic submucosal dissection bleeding: a single-center, propensity score-matched analysis.

OBJECTIVES: Both potassium-competitive acid blockers (P-CABs) and proton pump inhibitors (PPIs) are known to be protective against bleeding after gastric endoscopic dissection (ESD) for early gastric cancers. The aim was to compare the effect of PPI and P-CAB treatment against bleeding after gastric ESD. MATERIALS AND METHODS: This was a single-center, retrospective analysis. Among 541 patients who underwent gastric ESD during the period from 2014 to 2019, we recruited subjects who were treated with PPIs (intravenous lansoprazole followed by oral esomeprazole) or a P-CAB before and after ESD. The incidence of post-ESD bleeding was compared between treatment groups. The risks associated with post-ESD bleeding were examined by univariate and multivariate analyses after propensity score-matching. RESULTS: The overall incidence of post-ESD bleeding was not significantly different between patients treated with PPIs (n = 362) and those treated with a P-CAB (n = 156) (3.0% vs 2.6%, respectively; p = .77). Even after propensity score matching (n = 153 in each group), the incidence was not significantly different between groups (2.6% vs 2.6%, respectively; p = 1.00). A multivariate analysis revealed that antithrombotic therapy (OR 4.85, 95% CI 1.14-20.57) was an independent factor associated with post-ESD bleeding. CONCLUSIONS: The incidence of post gastric ESD bleeding is not different between patients treated with PPI and patients treated with P-CAB. Antithrombotic therapy is an independent risk factor associated with post-ESD bleeding.

Expression analysis of proteasome maturation protein (POMP) gene in Liaoning Cashmere goat.

Liaoning Cashmere goat is a precious genetic resource of China. To explore the relationship between POMP and cashmere growth, we analyzed the expression of POMP. POMP encodes a hudrophilic protein which is most closely related to bos. RT-PCR showed that POMP was expressed in skin, heart, liver, spleen, lung, and kidney tissues. Real-time PCR showed that the expression of POMP was more active in the secondary hair follicles than the primary hair follicles in anagen. In situ hybridization showed that POMP was obviously expressed in the Inner Root Sheath (IRS) but no expression in Outer Root. The treatment of fibroblasts with melatonin (MT), fibroblast growth factors 5 (FGF5) and insulin-like growth factors 1 (IGF-1) showed that MT/FGF5/IGF-1 much performance for inhibiting the expression of POMP; MT + FGF5 inhibited the expression of POMP; MT + IGF-1 promoted the expression of POMP. When Noggin expression is decreased by siRNA, the expression of POMP is inhibited. To sum up, POMP strongly expressed in the root sheath of hair follicles, related to the development of the primary and secondary hair follicle; In addition, by adding MT/FGF5/IGF-1 or interfering with the Noggin expression to regulate the expression of POMP, to control the growth of Liaoning Cashmere goat cashmere.

Gastro-pharyngeal reflux and total laryngectomy. Increasing knowledge about its management.

PURPOSE: Investigate the incidence, the degree and the effect of gastro-pharyngeal reflux (GPR) in laryngectomised patients. MATERIALS AND METHODS: Behavioral and 24-hour pH- and impedance-monitoring data were prospectively analyzed for 25 laryngectomised patients with no previous history of GER in outpateints' setting. Reflux detected was characterized as either acid, weakly acidic or nonacid. Proximal reflux was found at 15cm above the LES. RESULTS: 40% of patients presented a pathological number of reflux episodes in the upright position (p<0.0001); 9 of them presented a pathologic bolus exposure time. Bolus exposure at the proximal sphincter was one fourth-fold lower than 5cm above the LES (p=0.3593). There was a prevalence of acid reflux at both sphincters (p<0.0001); liquid reflux was prevalent at the LES (p=0.003) and mixed reflux at the UES (p=0.0001). Median REs was higher than time acid exposure (p=0.0013). CONCLUSIONS: Pre- and post-surgical reflux investigation could identify preexisting reflux severity and screen potential high-risk cancer patients for postoperative complications. This might allow the early onset of acid suppressive therapy in presence of pathologic findings in high-complication risk cancer patients.

Models and analyses to understand threats to polio eradication.

To achieve complete polio eradication, the live oral poliovirus vaccine (OPV) currently used must be phased out after the end of wild poliovirus transmission. However, poorly understood threats may arise when OPV use is stopped. To counter these threats, better models than those currently available are needed. Two articles recently published in BMC Medicine address these issues. Mercer et al. (BMC Med 15:180, 2017) developed a statistical model analysis of polio case data and characteristics of cases occurring in several districts in Pakistan to inform resource allocation decisions. Nevertheless, despite having the potential to accelerate the elimination of polio cases, their analyses are unlikely to advance our understanding OPV cessation threats. McCarthy et al. (BMC Med 15:175, 2017) explored one such threat, namely the emergence and transmission of serotype 2 circulating vaccine derived poliovirus (cVDPV2) after OPV2 cessation, and found that the risk of persistent spread of cVDPV2 to new areas increases rapidly 1-5 years after OPV2 cessation. Thus, recently developed models and analysis methods have the potential to guide the required steps to surpass these threats. 'Big data' scientists could help with this; however, datasets covering all eradication efforts should be made readily available.Please see related articles: https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-017-0937-y and https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-017-0941-2 .

Multislice CEST MRI improves the spatial assessment of tumor pH.

PURPOSE: Multislice maps of extracellular pH (pHe) are needed to interrogate the heterogeneities of tumors and normal organs. To address this need, we have developed a multislice chemical exchange saturation transfer (CEST) MRI acquisition method with a CEST spectrum-fitting method that measures in vivo pHe over a range of 6.3 to 7.4. METHODS: The phase offset multiplanar (POMP) method was adapted for CEST fast imaging with steady-state free precession (FISP) MRI to acquire multiple image slices with a single CEST saturation pulse. The Bloch-McConnell equations were modified to include pH based on a calibration of pH and chemical exchange rate for the contrast agent iopamidol. These equations were used to estimate the pixel-wise pHe values throughout the multislice acidoCEST MR images of the tumor, kidney, bladder, and other tissues of a MDA-MB-231 tumor model. RESULTS: Multislice acidoCEST MRI successfully mapped a gradient of pHe from 6.73 to 6.81 units from the tumor core to rim, and also mapped a gradient of pHe 6.56 to 6.97 across the mouse kidney. The bladder was found to be pHe 6.3. CONCLUSION: AcidoCEST MRI with POMP acquisition and Bloch-McConnel analysis can map pHe in multiple imaging slices through the tumor, kidney, and bladder. This multislice evaluation facilitates assessments of spatial heterogeneity of tissue pHe. Magn Reson Med 78:97-106, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Questionnaire-based survey in a developing country showing noncompliance with paediatric gastro-oesophageal reflux practice guidelines.

AIM: This 2015 study investigated whether Lebanese paediatricians diagnosed and managed gastro-oesophageal reflux disease (GERD) in infants and children in accordance with the 2009 guidelines from the North American and European Societies for Paediatric Gastroenterology, Hepatology and Nutrition. METHODS: Paediatricians members of the Lebanese Order of Physicians with updated email addresses were invited to complete a web-based survey between September and November 2015, to assess their knowledge and management of GERD. RESULTS: Responses were received from 114 of the 543 paediatricians, and 96 were analysed. Only two respondents complied fully with the international guidelines. The majority diagnosed GERD in infants based solely on their medical history and examination. Moreover, nearly two-thirds of the respondents would start an empiric trial with acid suppression. Around half of the respondents considered proton pump inhibitors to be the mainstay of GERD treatment. CONCLUSION: This was the first Lebanese study that surveyed the management of paediatric GERD. Only 2.1% of the paediatricians followed the guidelines on the evidence-based management of GERD. This highlights the need for studies to assess barriers to guideline implementation and the development of new guidelines accounting for regional factors, mainly the cost of investigations and prevalence of medical insurance.

MCM3AP and POMP Mutations Cause a DNA-Repair and DNA-Damage-Signaling Defect in an Immunodeficient Child.

Immunodeficiency patients with DNA repair defects exhibit radiosensitivity and proneness to leukemia/lymphoma formation. Though progress has been made in identifying the underlying mutations, in most patients the genetic basis is unknown. Two de novo mutated candidate genes, MCM3AP encoding germinal center-associated nuclear protein (GANP) and POMP encoding proteasome maturation protein (POMP), were identified by whole-exome sequencing (WES) and confirmed by Sanger sequencing in a child with complex phenotype displaying immunodeficiency, genomic instability, skin changes, and myelodysplasia. GANP was previously described to promote B-cell maturation by nuclear targeting of activation-induced cytidine deaminase (AID) and to control AID-dependent hyperrecombination. POMP is required for 20S proteasome assembly and, thus, for efficient NF-κB signaling. Patient-derived cells were characterized by impaired homologous recombination, moderate radio- and cross-linker sensitivity associated with accumulation of damage, impaired DNA damage-induced NF-κB signaling, and reduced nuclear AID levels. Complementation by wild-type (WT)-GANP normalized DNA repair and WT-POMP rescued defective NF-κB signaling. In conclusion, we identified for the first time mutations in MCM3AP and POMP in an immunodeficiency patient. These mutations lead to cooperative effects on DNA recombination and damage signaling. Digenic/polygenic mutations may constitute a novel genetic basis in immunodeficiency patients with DNA repair defects.

The Nuclear Factor (Erythroid-derived 2)-like 2 and Proteasome Maturation Protein Axis Mediate Bortezomib Resistance in Multiple Myeloma.

Resistance to the proteasome inhibitor bortezomib is an emerging clinical problem whose mechanisms have not been fully elucidated. We considered the possibility that this could be associated with enhanced proteasome activity in part through the action of the proteasome maturation protein (POMP). Bortezomib-resistant myeloma models were used to examine the correlation between POMP expression and bortezomib sensitivity. POMP expression was then modulated using genetic and pharmacologic approaches to determine the effects on proteasome inhibitor sensitivity in cell lines and in vivo models. Resistant cell lines were found to overexpress POMP, and while its suppression in cell lines enhanced bortezomib sensitivity, POMP overexpression in drug-naive cells conferred resistance. Overexpression of POMP was associated with increased levels of nuclear factor (erythroid-derived 2)-like (NRF2), and NRF2 was found to bind to and activate the POMP promoter. Knockdown of NRF2 in bortezomib-resistant cells reduced POMP levels and proteasome activity, whereas its overexpression in drug-naive cells increased POMP and proteasome activity. The NRF2 inhibitor all-trans-retinoic acid reduced cellular NRF2 levels and increased the anti-proliferative and pro-apoptotic activities of bortezomib in resistant cells, while decreasing proteasome capacity. Finally, the combination of all-trans-retinoic acid with bortezomib showed enhanced activity against primary patient samples and in a murine model of bortezomib-resistant myeloma. Taken together, these studies validate a role for the NRF2/POMP axis in bortezomib resistance and identify NRF2 and POMP as potentially attractive targets for chemosensitization to this proteasome inhibitor.

Effect of long-term proton pump inhibitors on phosphocalcium metabolism and bone mineral density.

Aim: Although Proton pump inhibitors (PPIs) are well-tolerated, their long-term use may be associated with decreased bone mass. Methods: This is a case-control study including patients treated with PPIs (>1 year) and control subjects who have not received PPIs treatment. Results: A total of 90 patients and 90 matched controls were included. PPIs use was associated with hypocalcemia and hypomagnesemia. Vitamin D3 deficiency and hyperparathyroidism were associated with PPIs use. Long-term PPIs use was significantly associated with decreased bone density. Risk factors of decreased bone mineral density (BMD) included age >50 years, menopause, lack of sun exposure, double PPIs dose, daily intake, post-meal intake and association with a mucoprotective agent. Conclusion: Our results highlight the risk of decreased BMD in patients on long-term PPIs treatment.

In this study, we investigated the impact of long-term use of proton pump inhibitors (PPIs) on bone health. Examining 90 patients on PPIs for over a year and matching them with control subjects, we found that PPIs were linked to lower bone density. Factors such as age over 50. menopause, limited sun exposure, higher PPIs dosage, daily intake, post-meal usage and combining PPIs with a mucoprotective agent were associated with decreased bone mineral density. Our findings emphasize the concern of reduced bone density in individuals undergoing prolonged PPIs treatment.

The efficacy and safety of itopride as an add-on therapy to a proton pump inhibitor in the treatment of gastroesophageal reflux disease.

Introduction: The primary objective was to demonstrate the efficacy and safety of itopride as an add-on therapy to a proton pump inhibitor (PPI) in the treatment of gastroesophageal reflux disease. Aim: Reflux disease affects the largest percentage of the population worldwide, symptoms overlap with many other conditions which hamper diagnostic and therapy presenting challenges in treating patients and prompting an intensive search for new, more effective therapeutic regimens. Material and methods: A retrospective study was undertaken with 140 enrolled patients with reflux disease, confirmed by 24-hour pH impedance previously treated with PPIs without any significant improvement. Itopride was added to the PPI therapy in a dose of 150 mg/day, after which the severity of reflux disease symptoms was reassessed. Results: The greatest improvement after the combined treatment (p < 0.001) was experienced in the context of heartburn, nausea and laryngopharyngeal symptoms. There was also a high percentage of statistically significant (p < 0.01) improvement in burning in the oesophagus and stomach and regarding postprandial fullness, gastric retention and swallowing disorders. No adverse effects were noted. Conclusions: The presented study clearly demonstrates that in patients ineffectively treated with PPIs, the addition of itopride to the therapy for 8 weeks without changing the PPI dose, significantly improves the efficacy of treatment of reflux disease and thus shortens the need for medication usage and reduces the costs of therapy, potential side effects of PPI, improves the patient's quality of life and decreases the frequency of medical appointments.

Visualizing chaperone-mediated multistep assembly of the human 20S proteasome.

Dedicated assembly factors orchestrate stepwise production of many molecular machines, including the 28-subunit proteasome core particle (CP) that mediates protein degradation. Here, we report cryo-EM reconstructions of seven recombinant human subcomplexes that visualize all five chaperones and the three active site propeptides across a wide swath of the assembly pathway. Comparison of these chaperone-bound intermediates and a matching mature CP reveals molecular mechanisms determining the order of successive subunit additions, and how proteasome subcomplexes and assembly factors structurally adapt upon progressive subunit incorporation to stabilize intermediates, facilitate the formation of subsequent intermediates, and ultimately rearrange to coordinate proteolytic activation with gated access to active sites. The structural findings reported here explain many previous biochemical and genetic observations. This work establishes a methodologic approach for structural analysis of multiprotein complex assembly intermediates, illuminates specific functions of assembly factors, and reveals conceptual principles underlying human proteasome biogenesis.

Evolution of pyruvate kinase-deficient Escherichia coli mutants enables glycerol-based cell growth and succinate production.

AIMS: The aim of this study was to engineer Escherichia coli strains that efficiently produce succinate from glycerol under anaerobic conditions after an aerobic growth phase. METHODS AND RESULTS: We constructed E. coli strain ss195 with deletions of pykA and pykF, which resulted in slow growth on glycerol as sole carbon source. This growth defect was overcome by the selection of fast-growing mutants. Whole-genome resequencing of the evolved mutant ss251 identified the mutation A595S in PEP carboxylase (Ppc). Reverse metabolic engineering by introducing the wild-type allele revealed that this mutation is crucial for the described phenotype. Strain ss251 and derivatives thereof produced succinate with high yields above 80% mol mol(-1) from glycerol under nongrowth conditions. CONCLUSIONS: The results show that during the aerobic growth of ss251, the formation of pyruvate proceeds via the proposed POMP pathway, starting with the carboxylation of PEP by Ppc. The resulting oxaloacetate is reduced by malate dehydrogenase (Mdh) to malate, which is then decarboxylated back to pyruvate by a malic enzyme (MaeA or MaeB). Mutation of ppc is crucial for fast growth of pykAF mutants on glycerol. SIGNIFICANCE AND IMPACT OF STUDY: An E. coli mutant that is capable of achieving high yields of succinate (a top valued-added chemical) from glycerol (an abundant carbon source) was constructed. The identified ppc mutation could be applied to other production strains that require strong PEP carboxylation fluxes.

A case of colonic perforation in collagenous colitis without diarrheal symptoms.: A case report.

INTRODUCTION: Collagenous colitis is an inflammatory disease characterized by hyperplasia of the collagen band beneath the colonic mucous membrane. Chronic diarrhea is a characteristic clinical symptom. The disease is often diagnosed accidentally on colonoscopy for chronic diarrhea, and patients without chronic diarrhea have few chances to suspect the disease. PRESENTATION OF CASE: The patient was a 75-year-old woman. The chief complaint was sudden upper abdominal pain and vomiting. There were no important findings regarding the consumed food or bowel habits (no diarrhea). Computed tomography revealed wall thickness and a small amount of free air around the descending colon. An emergency laparotomy was performed with the diagnosis of spontaneous colonic perforation. Intra-operative findings revealed a longitudinal ulcer and micro-perforation to the mesenterial side at the descending colon. Pathological findings revealed subepithelial collagenous band in the submucosal background of the ulcer, and which was diagnosed as collagenous colitis. DISCUSSION: Intestinal perforation in collagenous colitis is extremely rare. It was considered that perforation was caused by a transient increase in intestinal pressure in the background of collagenous colitis. Further, to the best of our knowledge, this is the first report of a critical case which presented without the characteristic symptom of chronic diarrhea. CONCLUSION: We report a rare case of colonic perforation of the collagenous colitis.

Impact of proton pump inhibitors on the onset of gastrointestinal immune-related adverse events during immunotherapy.

INTRODUCTION: The gut microbiota (GM) can influence the pathogenesis of immune-mediated adverse events (irAEs). Proton pump inhibitors (PPIs) can affect the integrity of GM, but their role in promoting irAEs is still poorly understood. METHODS: In this retrospective single-center cohort study, the primary endpoint was the evaluation of the incidence of gastrointestinal (GI) irAEs in cancer patients on PPIs (exposed) versus cancer patients who were not on PPIs (unexposed). RESULTS: Three hundred and sixty three patients' records (248 M/115F, median age 69) were reviewed. Twenty-three exposed patients (92%) developed GI irAEs while only two unexposed patients (8%) developed GI irAEs (hazard ratio [HR] 13.22, 95% confidence interval [CI] 3.11-56.10, p < 0.000). This HR was confirmed after weighting for the propensity score (HR15.13 95% CI 3.22-71.03, p < 0.000). CONCLUSION: Chronic PPI use is associated with an increased risk of GI irAES.

Convulsive Seizure Due to Hypomagnesemia Caused by Short-term Vonoprazan Intake.

A 71-year-old woman was admitted for the treatment of diffuse large B-cell lymphoma of the ileum. She had been taking lansoprazole but was switched to vonoprazan due to epigastric discomfort. Three weeks after starting vonoprazan intake, she had a convulsive seizure, and a blood test showed hypomagnesiemia. The cause of hypomagnesemia was considered to be malabsorption of magnesium from the intestinal tract associated with vonoprazan. After discontinuation of vonoprazan, the magnesium level quickly recovered, and the seizures did not relapse. It is important to consider the risk of hypomagnesemia in patients taking vonoprazan, even for a short period of time.

Deficient immunoproteasome assembly drives gain of α-synuclein pathology in Parkinson's disease.

Aberrant α-synuclein (α-Syn) accumulation resulting from proteasome dysfunction is considered as a prominent factor to initiate and aggravate the neurodegeneration in Parkinson's disease (PD). Although the involvement of 26S proteasome in proteostasis imbalance has been widely accepted, our knowledge about the regulation of immunoproteasome function and its potential role in α-Syn pathology remains limited. Immunoproteasome abundance and proteolytic activities depend on the finely tuned assembly process, especially ß-ring formation mediated by the only well-known chaperone proteasome maturation protein (POMP). Here, we identified that α-Syn overexpression was associated with a reduction in immunoproteasome function, which in turn limited the degradation of polo-like kinase 2 (PLK2), exacerbated α-Syn Ser129 phosphorylation and aggregation, ultimately leading to the neurodegeneration. These effects could be dramatically attenuated by ß5i overexpression. Mechanistically, α-Syn suppressed the transcriptional regulation of POMP by nuclear factor erythroid 2-related factor 2 (NRF2), thereby preventing the assembly of immunoproteasome ß subunits. Dopaminergic neurons-specific overexpression of NRF2-POMP axis effectively rescued the aggregation of α-Syn and PD-like phenotypes. These findings characterized abnormal immunoproteasome assembly as a key contributor governing α-Syn accumulation and neurodegeneration, which might open up a new perspective for the implication of immunoproteasome in PD and provide approaches of manipulating immunoproteasome assembly for therapeutic purposes.

Prognostic Value of Resistance Proteins in Plasma Cells from Multiple Myeloma Patients Treated with Bortezomib-Based Regimens.

While multiple myeloma (MM) treatment with proteasome inhibitors and other agents yields encouraging results, primary and secondary resistance remains an emerging problem. An important factor in such treatment resistance is the overexpression of several proteins. The present study comprehensively evaluates the expression of POMP, PSMB5, NRF2, XBP1, cMAF and MAFb proteins in plasma cells isolated from the bone marrow of 39 MM patients treated with bortezomib-based regimens using an enzyme-linked immunosorbent assay (ELISA). The proteins were selected on the basis of previous laboratory and clinical studies in bortezomib-treated MM patients. It was found that the expression of the investigated proteins did not significantly differ between bortezomib-sensitive and bortezomib-refractory patients. However, the expression of some proteins correlated with overall survival (OS); this was significantly shorter in patients with higher POMP expression (HR 2.8, 95% CI: 1.1-7.0, p = 0.0277) and longer in those with higher MAFB expression (HR 0.32, 95% CI: 0.13-0.80, p = 0.0147). Our results indicate that a high expression of POMP and MAFB in MM plasma cells may serve as predictors of OS in MM patients treated with bortezomib-based regimens. However, further studies are needed to determine the role of these factors in effective strategies for improving anti-myeloma therapy.

Phylogenetic and molecular analysis based on genes 16S-rRNA, OMPA and POMP to identify Chlamydia abortus infection occurrence at the milk samples of goats and sheep in west Azerbaijan of Iran.

BACKGROUND AND OBJECTIVES: Enzootic abortion in sheep and goats, also called ovine enzootic abortion (OEA) or enzootic abortion of ewes (EAE), is caused by Chlamydia abortus. The disease has a major economic impact as it represents the most important cause of lamb loss in sheep in parts of Europe, North America and Africa. This serious and potentially life-threatening zoonosis can also affect pregnant women after contact with lambing ewes, leading to severe febrile illness in pregnancy and loss of the foetus. MATERIALS AND METHODS: The present study was conducted to the Phylogenetic and Molecular Analysis based on Genes 16S-rRNA, OmpA and POMP of C. abortus in milk samples collected from sheep and goats in West Azerbaijan province, Iran. During 2018, a total number of 360 milk samples were collected from sheep (n = 180) and goats (n = 180) of different regions of the province. All milk samples were subjected to DNA extraction and examined by PCR. RESULTS: Among 360 milk samples collected from sheep and goats, 31 (8.611%; 95% CI=6.13-11.96) were positive for Chlamydia spp. The helicase, 16S-rRNA and ompA genes were examined and resulted in 8, 31, 31 of positive samples respectively. The accession numbers have been deposited in GenBank (NCBI) (MT367602 and MT367603). CONCLUSION: Phylogenetic analysis based on the gene of helicase showed that most of the isolates shared similarity > 99.97%.

The Prognostic Value of Whole-Blood PSMB5, CXCR4, POMP, and RPL5 mRNA Expression in Patients with Multiple Myeloma Treated with Bortezomib.

Proteasome inhibitors, like bortezomib, play a key role in the treatment of multiple myeloma (MM); however, most patients eventually relapse and eventually show multiple drug resistance, and the molecular mechanisms of this resistance remain unclear. The aim of our study is to assess the expression of previously described genes that may influence the resistance to bortezomib treatment at the mRNA level (ABCB1, CXCR4, MAF, MARCKS, POMP, PSMB5, RPL5, TXN, and XBP1) and prognosis of MM patients. mRNA expression was determined in 73 MM patients treated with bortezomib-based regimens (30 bortzomib-sensitive and 43 bortezomib-refractory patients) and 11 healthy controls. RPL5 was significantly down-regulated in multiple myeloma patients as compared with healthy controls. Moreover, POMP was significantly up-regulated in MM patients refractory to bortezomib-based treatment. In multivariate analysis, high expression of PSMB5 and CXCR and autologous stem cell transplantation were independent predictors of progression-free survival, and high expression of POMP and RPL5 was associated with shorter overall survival.