The Expression of a Subset of Aging and Antiaging Markers Following the Chondrogenic and Osteogenic Differentiation of Mesenchymal Stem Cells of Placental Origin.

Mesenchymal stem cells (MSCs) of placental origin hold great promise in tissue engineering and regenerative medicine for diseases affecting cartilage and bone. However, their utility has been limited by their tendency to undergo premature senescence and phenotypic drift into adipocytes. This study aimed to explore the potential involvement of a specific subset of aging and antiaging genes by measuring their expression prior to and following in vitro-induced differentiation of placental MSCs into chondrocytes and osteoblasts as opposed to adipocytes. The targeted genes of interest included the various LMNA/C transcript variants (lamin A, lamin C, and lamin A∆10), sirtuin 7 (SIRT7), and SM22α, along with the classic aging markers plasminogen activator inhibitor 1 (PAI-1), p53, and p16INK4a. MSCs were isolated from the decidua basalis of human term placentas, expanded, and then analyzed for phenotypic properties by flow cytometry and evaluated for colony-forming efficiency. The cells were then induced to differentiate in vitro into chondrocytes, osteocytes, and adipocytes following established protocols. The mRNA expression of the targeted genes was measured by RT-qPCR in the undifferentiated cells and those fully differentiated into the three cellular lineages. Compared to undifferentiated cells, the differentiated chondrocytes demonstrated decreased expression of SIRT7, along with decreased PAI-1, lamin A, and SM22α expression, but the expression of p16INK4a and p53 increased, suggesting their tendency to undergo premature senescence. Interestingly, the cells maintained the expression of lamin C, which indicates that it is the primary lamin variant influencing the mechanoelastic properties of the differentiated cells. Notably, the expression of all targeted genes did not differ from the undifferentiated cells following osteogenic differentiation. On the other hand, the differentiation of the cells into adipocytes was associated with decreased expression of lamin A and PAI-1. The distinct patterns of expression of aging and antiaging genes following in vitro-induced differentiation of MSCs into chondrocytes, osteocytes, and adipocytes potentially reflect specific roles for these genes during and following differentiation in the fully functional cells. Understanding these roles and the network of signaling molecules involved can open opportunities to improve the handling and utility of MSCs as cellular precursors for the treatment of cartilage and bone diseases.

Myelodysplastic Syndromes and Myelodysplastic Syndromes/Myeloproliferative Neoplasms: A Real-World Experience From a Developing Country.

PURPOSE: Myelodysplastic syndromes (MDS) include a heterogeneous group of clonal bone marrow disorders characterized by ineffective hematopoiesis. They manifest as dysplasia in bone marrow hemopoietic elements associated with peripheral cytopenias with variable risk of AML transformation. PATIENTS AND METHODS: We analyzed retrospectively registry data collected prospectively from patients with primary MDS and patients with MDS/myeloproliferative neoplasm (MPN) in the Jordan University Hospital between January 2007 and September 2021. The registry captured epidemiologic information such as date of diagnosis, age, gender, date of AML transformation, cytogenetics, MDS subtype, risk group according to Revised International Prognostic Scoring System, and survival. The registry also captured baseline ferritin, B12, and lactate dehydrogenase levels. RESULTS: A total of 112 patients with MDS and MDS/MPN were included in the registry. Median age at diagnosis was 59 years. The male-to-female ratio was about 1.2. In a multivariate cox regression model, baseline serum ferritin significantly affected survival as patients with levels exceeding 1,000 µg/L had a risk of death three times higher compared with those with <1,000 µg/L levels (P < .05). CONCLUSION: To our knowledge, our study is the first comprehensive study examining the epidemiology and prognostic factors in patients with MDS and patients with MDS/MPN in Jordan. Our results show that MDS and MDS/MPN epidemiology in Jordan is different compared with Western countries. Our results also show that baseline serum ferritin levels can be used as a prognostic marker for patients with MDS.

A Rare Case of Guillain-Barré Syndrome Post-gastrojejunostomy and Literature Review.

Guillain-Barré syndrome (GBS) is a rare immune-mediated neuropathy causing destruction of the peripheral nervous system, with molecular mimicry playing a major role in its pathophysiology. Despite its rarity, it is considered the most common cause of acute flaccid neuromuscular paralysis in the United States. Although diagnosing GBS depends on the clinical presentation of the patient, cerebrospinal fluid sampling, nerve conduction studies, electromyography, magnetic resonance imaging, and ganglioside antibody screening can be used to confirm the diagnosis and rule out other differentials. Here, we report a rare case of GBS as a postoperative complication after a successful gastrojejunostomy to excise an adenocarcinoma in the second part of the duodenum. Such a complication is rare and not fully understood yet.

Rosai-Dorfman Disease: Case Series and Literature Review.

Rosai-Dorfman Disease (RDD), also known as sinus histiocytosis with massive lymphadenopathy, is an uncommon histiocytic condition characterized by massive histopathological aggregation of CD1-a negative, CD68-positive, and S100-positive histiocytes. It was initially described by Destombes in 1965 under the term "adenitis with lipid excess." However, it is named after Rosai and Dorfman who reported further histopathological features of the disease in 1969. The diagnosis of this non-Langerhans cell histiocytosis can be challenging and requires high clinical suspicion. The diagnostic process usually involves imaging, tissue biopsies, and genetic testing as needed. In this case series, we are presenting three cases of rare disease. Case 2 had both nodal and extranodal forms, which makes this case rarer than cases 1 and 3, which present with extranodal lesions.

Real World Multiple Myeloma Registry from Jordan, a Developing Country.

Background and objective: Scanty reports from the middle east and north Africa (MENA) region have been published on multiple myeloma (MM). Multiple myeloma registry has been established at Jordan University Hospital (JUH) since 2009. Our work aims to review this Multiple Myeloma registry with data from 113 patients diagnosed with MM at JUH and analyze their management and course. Methods: This is a non-interventional and retrospective analysis of the MM registry from 2009-to 2016 involving 113 patients at JUH. Statistical analysis was done using the Statistical Package for the Social Sciences (SPSS). Overall survival (OS) was analyzed with the Kaplan-Meier method. P-value was considered significant if it was (<0.05). Results: We found no gender difference in this registry. The median age is 62 years. Most patients are in ISS stage II and III (36.28% for each). Immunoglobulin type G Kappa is the dominant subtype. Bone pain is the most common presenting symptom. The most common laboratory finding is anemia (45.6%). Most of our patients (85.2%) had received thalidomide and dexamethasone, while only 14.8% received bortezomib, thalidomide, and dexamethasone. Our patients' mean overall survival (OS) was 74 months, and the median survival was 38 months. For ISS stages I, II, and III, median OS was 96, 46, and 16 months. Conclusion: MM in a developing country presents a challenging disease compared to industrial countries in both epidemiology and management. An improved road map in the care of MM in these countries is needed. The use of three or four drugs combination upfront is warranted. However, this is limited because of the high cost of these drugs. We expect the following decade to show better survival and quality of life for MM patients once these drugs are widely used.

DNA hypermethylation of cell cycle (p15 and p16) and apoptotic (p14, p53, DAPK and TMS1) genes in peripheral blood of leukemia patients.

Aberrant DNA methylation of tumor suppressor genes has been reported in all major types of leukemia with potential involvement in the inactivation of regulatory cell cycle and apoptosis genes. However, most of the previous reports did not show the extent of concurrent methylation of multiple genes in the four leukemia types. Here, we analyzed six key genes (p14, p15, p16, p53, DAPK and TMS1) for DNA methylation using methylation specific PCR to analyze peripheral blood of 78 leukemia patients (24 CML, 25 CLL, 12 AML, and 17 ALL) and 24 healthy volunteers. In CML, methylation was detected for p15 (11%), p16 (9%), p53 (23%) and DAPK (23%), in CLL, p14 (25%), p15 (19%), p16 (12%), p53 (17%) and DAPK (36%), in AML, p14 (8%), p15 (45%), p53 (9%) and DAPK (17%) and in ALL, p15 (14%), p16 (8%), and p53 (8%). This study highlighted an essential role of DAPK methylation in chronic leukemia in contrast to p15 methylation in the acute cases, whereas TMS1 hypermethylation was absent in all cases. Furthermore, hypermethylation of multiple genes per patient was observed, with obvious selectiveness in the 9p21 chromosomal region genes (p14, p15 and p16). Interestingly, methylation of p15 increased the risk of methylation in p53, and vice versa, by five folds (p=0.03) indicating possible synergistic epigenetic disruption of different phases of the cell cycle or between the cell cycle and apoptosis. The investigation of multiple relationships between methylated genes might shed light on tumor specific inactivation of the cell cycle and apoptotic pathways.

Brucellosis presenting as myelofibrosis: first case report.

We describe the case of a 29-year-old woman who presented with pancytopenia and myelofibrosis. Brucella melitensis was identified in her blood. The patient recovered completely with doxycycline and rifampin. A repeat bone marrow biopsy showed hypercellularity without myelofibrosis. Bone marrow findings in cases of pancytopenia due to brucellosis reveal normocellularity, hypercellularity, hemophagocytosis, or granuloma. To our knowledge this is the first report of brucellosis causing myelofibrosis. Brucellosis should be considered as a possible cause of myelofibrosis in endemic areas.

Primary myelodysplastic syndrome in Jordan: a single-centre experience.

OBJECTIVE: Study of the disease patterns and clinical evaluation of myelodysplastic syndrome (MDS). SUBJECTS AND METHODS: A retrospective analysis was carried out on 85 patients, with MDS who were followed up over a period of 23 years at Jordan University Hospital, Amman, Jordan. Cases were analyzed according to the French, American and British Classification. RESULTS: Of the 85 patients, 42 (49.4%) were females and 43 (50%) males; mean age was 59 +/- 19 years (range 18-88). Most subtypes found in patients were refractory anemia (RA) in 27 (31.8%) and RA with excess blasts (RAEB) in 28 (32.9%). Adverse prognostic indicators were RAEB subtype and requirement for blood transfusion. CONCLUSION: Our findings showed that MDSs appeared at a younger age and tended to be of the aggressive subtype. Chronic myelomonocytic leukemia subtype seemed to appear dominantly in men.