Interleukin-7 Biology and Its Effects on Immune Cells: Mediator of Generation, Differentiation, Survival, and Homeostasis

Interleukin-7 (IL-7), a molecule known for its growth-promoting effects on progenitors of B cells, remains one of the most extensively studied cytokines. It plays a vital role in health maintenance and disease prevention, and the congenital deficiency of IL-7 signaling leads to profound immunodeficiency. IL-7 contributes to host defense by regulating the development and homeostasis of immune cells, including T lymphocytes, B lymphocytes, and natural killer (NK) cells. Clinical trials of recombinant IL-7 have demonstrated safety and potent immune reconstitution effects. In this article, we discuss IL-7 and its functions in immune cell development, drawing on a substantial body of knowledge regarding the biology of IL-7. We aim to answer some remaining questions about IL-7, providing insights essential for designing new strategies of immune intervention.

Two New Cases of Primary Microcephaly with Neuronal Migration Defect Caused by Truncating Mutations in the ASPM Gene

Autosomal recessive primary microcephaly (MCPH) is a uncommon disorder due to congenital deficiency in the development of the cerebral cortex, characterized by a head circumference below 2 SD. MCPH is a group of diseases with genetic heterogeneity and has been reported by the Online Mendelian Inheritance In Man® (OMIM) database and associated with 25 different genes. It is known that MCPH cases are most frequently associated with abnormal spindle-like, microcephaly-associated (<i>ASPM</i>) gene mutations. The ASPM protein consists of an N-terminal 81 IQ (isoleucine-glutamine) domain, a calponin-homology domain, and a C-terminal domain. It interacts with calmodulin and calmodulin-related proteins via the IQ domain and acts as a part in mitotic spindle function. The basic characteristics of cases with <i>ASPM</i> gene mutations are microcephaly (below <b>−</b>3 SD) present before 1 year of age, intellectual disability, and the absence of other congenital anomalies. Macroscopic organization of the brain is preserved in cases with <i>ASPM</i> mutation, and a decrease in brain volume, particularly gray matter volume loss and a simplified gyral pattern are observed. Cortical migration defects are a very rare finding in patients with <i>ASPM</i> mutations. In the present study, we aimed to discuss the clinical and genetic findings in 2 cases with cortical dysplasia in which truncated variants in the <i>ASPM</i> gene were detected, particularly in terms of genotype-phenotype correlation in comparison with the literature.

Congenital Deficiency of Conventional Dendritic Cells Promotes the Development of Atopic Dermatitis-Like Inflammation

Atopic dermatitis (AD) is a common pruritic inflammatory skin disease characterized by impaired epidermal barrier function and dysregulation of Thelper-2 (TH2)-biased immune responses. While the lineage of conventional dendritic cells (cDCs) are implicated to play decisive roles in T-cell immune responses, their requirement for the development of AD remains elusive. Here, we describe the impact of the constitutive loss of cDCs on the progression of AD-like inflammation by using binary transgenic (Tg) mice that constitutively lacked CD11chi cDCs. Unexpectedly, the congenital deficiency of cDCs not only exacerbates the pathogenesis of AD-like inflammation but also elicits immune abnormalities with the increased composition and function of granulocytes and group 2 innate lymphoid cells (ILC2) as well as B cells possibly mediated through the breakdown of the Fms-related tyrosine kinase 3 ligand (Flt3L)-mediated homeostatic feedback loop. Furthermore, the constitutive loss of cDCs accelerates skin colonization of Staphylococcus aureus (S. aureus), that associated with disease flare. Thus, cDCs maintains immune homeostasis to prevent the occurrence of immune abnormalities to maintain the functional skin barrier for mitigating AD flare.

Deformity Reconstruction Surgery for Tibial Hemimelia

Tibial hemimelia is a rare congenital deficiency with a wide spectrum of pathology and deformity. This paper aims to give a comprehensive review of tibial hemimelia, with a concise summary of the history, pathology, and clinical findings of tibial hemimelia, while providing treatment recommendations and a review of the current literature. Classifications and surgical treatments are discussed, including amputation, limb reconstruction, and lengthening. Type-specific treatments are also discussed, including staged distraction correction of joint contractures of knee and ankle, Weber patelloplasty, fibular centralization, knee and ankle arthrodesis, implantable articulated distractors, and the role of femoral shortening. Amputation is a simpler and easier solution for many patients; however, reconstruction options continue to evolve, improve, and provide better functional outcomes in many cases. Factors favoring surgical reconstruction include the presence of a knee joint/proximal tibia, and the presence of a patella and quadriceps mechanism.

Secondary prevention of thrombosis with direct oral anticoagulants for hereditary hematogenous thrombophilia

Aim. The article describes the experience of using direct oral anticoagulants – drugs Dabigatran, Rivaroxaban and Apixaban for the secondary prevention of thrombosis in patients with the most common variants of hereditary hematogenous thrombophilia.Materials and methods. 86 patients were under observation: 53 men, 33 women. Only the registered fact of thrombosis, thromboembolism, ischemia or organ infarction was the basis for the diagnosis of hematogenous thrombophilia and further secondary prevention of thrombosis. In 80 cases, there was a combined form of thrombophilia. In addition to hereditary factors, there were acquired thrombogenic factors. Dabigatran etexilate (Pradaxa®) for the prevention of thrombus formation was prescribed to 41 patients aged 20 to 60 years; duration of admission from 12 months to 9 years, the dose of the drug was selected individually from 150 to 300 mg per day. Rivaroxaban (Xarelto®) for the prevention of thrombus formation was prescribed to 25 patients aged 18 to 54 years, duration of admission from 12 months to 7 years, the dose of the drug is 10-20 mg per day. Apixaban (Eliquis®) was prescribed to 10 patients, aged 30 to 50 years, the duration of admission was from 6 months up to 2 years, dosage 5-10 mg per day. For hyperhomocysteinemia, Angiovit® or Pentavit® was prescribed. Protein C and antithrombin III preparations with their congenital deficiency were used according to indications.Results. After Dabigatran was prescribed, only one patient had a recurrent pulmonary embolism due to low adherence to treatment. In other patients who were prescribed direct oral anticoagulants, no recurrence of thrombotic complications was recorded. No hemorrhagic complications were diagnosed with the use of Dabigatran and Apixaban. In 5 patients receiving Rivaroxaban, there were minor epistaxis; in three cases they stopped when the dose was reduced from 20 to 15-10 mg, two patients were transferred to dabigatran. No life-threatening bleeding has been reported.Conclusion. Dabigatran, Rivaroxaban and Apixaban are effective and safe drugs for antithrombotic therapy. The absence of the need for constant laboratory monitoring and extremely rare hemorrhagic complications makes it possible to use them in patients living in areas remote from large medical centers. Only 10 patients under our supervision with a diagnosis of “hematogenous thrombophilia” are currently taking warfarin. Timely diagnosis of the variant of hematogenous thrombophilia and the appointment of adequate anti-thrombotic therapy contributes to the relapse-free course of the disease.

Rapid Identification of 44 Steroids in Human Urine Samples using HPLC-ESI-QTOF-MS

Objective: Detailed analysis of un-processed and un-derivatized free and conjugated urinary steroids is useful to avoid miscalculations and to diagnose sports doping and adrenal problems including abnormal steroidogenesis, congenital deficiency of related enzymes, cancer, and other disease conditions. Hence, the present study was conducted to develop a soft ionization method to identify the maximum number of urinary steroids using ultra-performance liquid chromatography coupled with quadrupole time of flight mass spectrometer (HPLC–Q-TOF-MS). Material and Methods: HPLC–Q-TOF-MS was carried out for the qualitative detection of steroids and their conjugates in urine samples. The method provides high sensitivity and fast analysis of steroids and their glucuronides without hydrolysis or sample preparation or extraction of steroids. Results: Using the method, 44 steroids belonging to C-18, C-19, and C-21 classes and their conjugates were resolved and identified using positive and negative modes of ionizations by their characteristic ionization and collision energy induced dissociation behaviors. Conclusion: The method is time-saving and good to compare samples from different peoples with control or healthy ones as it doesn’t require any kind of pre-treatment or sample processing. It provides a complete picture of steroids metabolism and catabolism. It can be good for doping control or to explore the effects of other drugs. However, in qualitative analysis one may miss the significant information unless direct methods of steroids analysis to be employed.