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This is a systematic attempt to depict the genetic evolution of the Late Quaternary sediments of the southeastern (SE) coastal region of the Bengal basin regarding paleotectonic settings, sedimentation, provenance, paleo-climatic conditions, weathering condition and age. The study has considered multiple attributes such as, lithology/lithofacies, sedimentary features/records, major oxides, clay minerals, foraminifera, and radiocarbon dating. The lithological characters along with associated clay minerals confirmed that a Pleistocene paleosol horizon (over-bank deposits) of warm-humid nature is commonly encountered immediately on top of the sub-crop bed-rock in the area overlain by Holocene fluvio-marine sediments of the same nature. The lithofacies, foraminiferal assemblages, and sedimentary structures of the analyzed samples suggest that the Holocene sediments have been presumably deposited in a fluvio-marine condition after the Last Glacial Maximum (LGM) due to the transgression of the sea. Geochemically, the sediments are classified as Fe-rich shale, shale, and wake and primarily intermediate to felsic orogen provenance. These are possibly derived from intense weathered sources from the upheaval of Himalayan ranges of both active continental margin and Island Arc paleotectonic setting. The plot of the Index of Compositional Variability versus the Chemical Index of Alteration indicates that the sediments seemingly experienced intense weathering associated with warm and humid climatic conditions. The sedimentation rates of the area vary from place to place and layer to layer due to the complex delta-building process. The reconstructed Relative Sea Level Curve reveals that presumably, the sea level has reached its current position after the LGM. The deduction possibly will facilitate the (1) reconstruction of Late Quaternary coastal evolution after LGM, (2) support for future urbanization, land use plans, etc., and (3) also be helpful for international researchers to understand the possible sources of sediment input in the area from the complex interplay of the Indian-, Eurasian- and Myanmar-plates., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background and Aims: Facial palsy is a rare complication of the COVID-19 infection. Herein, we conducted a systematic review of all published cases of facial palsy post-COVID-19 infection in an attempt to educate the general population and medical practitioners regarding the likely occurrence of facial palsy in COVID-19 patients, its detection, effective treatment plan, and prognosis of the condition., Methods: We searched PubMed, Google Scholar, and Directory of Open Access Journals (DOAJ) from December 1, 2019 to September 21, 2021., Results: We included 49 studies bearing accounts of 75 cases who had facial palsy. The mean age of patients was 42.9 ± 19.59 years, with a male-to-female ratio of 8:7. The majority of the cases were reported from Brazil ( n  = 14), USA ( n  = 9), Turkey ( n  = 9), and Spain ( n  = 9). Noticeably, 30.14% of COVID-19 patients were diagnosed with Guillain-Barré syndrome. In total, 22.97% of patients complained of bilateral facial paralysis ( n  = 17), whereas ipsilateral paralysis was observed in 77.03% ( n  = 57). These were common complaints of Lagophthalmos, otalgia, facial drooping, dysarthria, and compromised forehead wrinkling. The treatment regimen mainly included the use of corticosteroids ( n  = 51) (69.86%), antivirals ( n  = 23) (31.51%), IVIG ( n  = 18) (24.66%), antibiotics ( n  = 13) (17.81%), antiretroviral ( n  = 9) (12.33%), and antimalarial ( n  = 8) (10.96%) medications. In all, 35.62% of patients ( n  = 26) adhered to a combination of antiviral and corticosteroid-based therapy. Positive treatment outcomes were observed in 83.58% ( n  = 56) of cases. In contrast, 10 patients (14.93%) showed nonsignificant recovery, out of which 3 (4.48%) died from the disease., Conclusion: The association of facial palsy with COVID-19 is controversial and therefore requires further investigation and published work to confirm a causal relationship. However, physicians should not overlook the likelihood of facial palsy post-COVID-19 infection and treat it accordingly., Competing Interests: Abdulqadir J. Nashwan is an Editorial Board member of Health Science Reports and co‐author of this article. He is excluded from editorial decision‐making related to the acceptance of this article for publication in the journal. The remaining authors declare no conflict of interest., (© 2022 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

Microvillus inclusion disease (MVID), a lethal congenital diarrheal disease, results from loss of function mutations in the apical actin motor myosin VB (MYO5B). How loss of MYO5B leads to both malabsorption and fluid secretion is not well understood. Serum glucocorticoid-inducible kinase 1 (SGK1) regulates intestinal carbohydrate and ion transporters including cystic fibrosis transmembrane conductance regulator (CFTR). We hypothesized that loss of SGK1 could reduce CFTR fluid secretion and MVID diarrhea. Using CRISPR-Cas9 approaches, we generated R26 Cre ER;MYO5B f/f conditional single knockout (cMYO5BKO) and R26 Cre ER;MYO5B f/f ;SGK1 f/f double knockout (cSGK1/MYO5B-DKO) mice. Tamoxifen-treated cMYO5BKO mice resulted in characteristic features of human MVID including severe diarrhea, microvillus inclusions (MIs) in enterocytes, defective apical traffic, and depolarization of transporters. However, apical CFTR distribution was preserved in crypts and depolarized in villus enterocytes, and CFTR high expresser (CHE) cells were observed. cMYO5BKO mice displayed increased phosphorylation of SGK1, PDK1, and the PDK1 target PKCι in the intestine. Surprisingly, tamoxifen-treated cSGK1/MYO5B-DKO mice displayed more severe diarrhea than cMYO5BKO, with preservation of apical CFTR and CHE cells, greater fecal glucose and reduced SGLT1 and GLUT2 in the intestine. We conclude that loss of SGK1 worsens carbohydrate malabsorption and diarrhea in MVID.

Background: Osteoporotic vertebral compression fractures (OVCFs) increasingly occur with advancing age, and are associated with significant morbidity, mortality, and cost. We assessed the clinical efficacy, radiological, and functional outcomes for patients undergoing percutaneous vertebroplasty (PVP) due to OVCFs, with a special focus on the frequency of new vertebral compression fractures (VCFs)., Methods: This study, carried from 2018 to 2020, included 22 females and 4 males. They averaged 60.15 years of age (range, 50-70) were followed an average of 14.5 months (range 12-36 months), and had 30 VCFs between the T7-L2 levels. Multiple variables were studied, including; anterior vertebral height (AVH) and kyphotic angle (KA), new VCFs, and functional outcomes., Results: The postoperative Visual Analog Scale and Oswestry Disability Index were significantly reduced at 12 months after PVP. Improvements for AVH and KA were also statistically significant; 23 patients (88.46%) had a dramatic decrease in pain on post-operative day 1, while 3 patients (11.53%) had no decrease in pain after PVP on post-operative day 1-1 postoperative month. No major complications were observed except high incidence of cement leakage at 8 levels (26.67%) in 6 patients. Additionally, new VCFs occurred in 10 vertebrae in 8 patients (30.76%), involving 6 adjacent (60%), and 4 nonadjacent vertebrae (40%)., Conclusion: PVP is an effective procedure in the management of painful OVCFs refractory to medical treatment. These PVP procedures yield immediate vertebral stabilization, relieve pain, and restore function with minimal associated morbidity., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Surgical Neurology International.)

Purpose: To perform retrospective analysis of 75 post-operative disc space infections after open lumbar discectomy (OLD) and to assess the outcome of their medical and surgical management in a tertiary-level hospital., Methods: Records of 50 men and 25 women aged 26-65 (mean, 42.53) years who underwent treatment for post-operative discitis (POD) after single level OLD at L3-4 (n = 8), L4-5 (n = 42), L5-S1 (n = 25) level. The POD was diagnosed according to specific clinical signs, laboratory and radiographic investigations and all of them received initial intravenous antibiotics (IVA) for at least 4-6 weeks followed by oral ones. Successful responders (n = 55) were considered in Group-C and remainder [Group-S (n = 20)] were operated at least after 4 weeks of failure. Demographic data, clinical variables, hospital stay, duration of antibiotic treatment and post-treatment complications were collected from the hospital record and assessment before and after treatment were done by using visual analogue scale (VAS) and Japanese Orthopaedic Association (JOA) score. Comprehensive outcome was evaluated by modified criteria of Kirkaldy-Willis., Results: The mean follows up was 36.38 months. Significant improvement of mean VAS and JOA score was achieved in both conservative (76.36% satisfactory) and operative (90% satisfactory) groups although the difference was statistically insignificant., Conclusion: Although insignificant, early surgical intervention provided better results (e.g. functional outcomes, length of hospital stay and duration of antibiotic treatment therapy) than conventional conservative treatment in post-operative discitis.

Background: Recurrent lumbar disc herniation (RLDH) is a common complication following primary microdiscectomy. Notably, revision surgery for recurrent disc herniation typically warrants "aggressive discectomy (AD)" rather than microdiscectomy due to the marked changes in anatomy, including postoperative scar. Here, we prospectively evaluated clinical outcomes of 22 RLDH patients following secondary aggressive discectomy (AD)., Methods: Records of 15 males and seven females averaging 41.7 years of age (range 21-60) who developed RLDH following primary microdiscectomy at the L4-5 ( n = 12) and L5-S1 ( n = 10) levels were studied. All patients underwent secondary AD for recurrent lesions (2014-2019). Multiple clinical parameters were assessed for these 22 patients. Outcomes were evaluated an average of 28.8 months postoperatively and included assessment of visual analog scales (VASs) and Japanese Orthopedic Association (JOA) Scores., Results: The VAS scores for back and radicular pain significantly improved, as did the JOA scores following surgery in all 22 patients after secondary AD., Conclusion: The authors concluded that secondary conventional revision discectomy (e.g., AD) effectively and safely managed RLDH., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Surgical Neurology International.)

Background: Normally, physicians understand they have a duty to treat patients, and they perform accordingly consistent with codes of medical practice, standards of care, and inner moral motivation. In the case of COVID-19 pandemic in a developing country such as Bangladesh, however, the fact is that some physicians decline either to report for duty or to treat patients presenting with COVID-19 symptoms. At issue ethically is whether such medical practitioners are to be automatically disciplined for dereliction of duty and gross negligence; or, on the contrary, such physicians may legitimately claim a professional right of autonomous judgment, on the basis of which professional right they may justifiably decline to treat patients., Methods: This ethical issue is examined with a view to providing some guidance and recommendations, insofar as the conditions of medical practice in an under-resourced country such as Bangladesh are vastly different from medical practice in an industrialized nation such as the USA. The concept of moral dilemma as discussed by philosopher Michael Shaw Perry and philosopher Immanuel Kant's views on moral appeal to "emergency" are considered pertinent to sorting through the moral conundrum of medical care during pandemic., Results: Our analysis allows for conditional physician discretion in the decision to treat COVID-19 patients, i.e., in the absence of personal protective equipment (PPE) combined with claim of duty to family. Physicians are nonetheless expected to provide a minimum of initial clinical assessment and stabilization of a patient before initiating transfer of a patient to a "designated" COVID-19 hospital. The latter is to be done in coordination with the national center control room that can assure admission of a patient to a referral hospital prior to ambulance transport., Conclusions: The presence of a moral dilemma (i.e., conflict of obligations) in the pandemic situation of clinical care requires institutional authorities to exercise tolerance of individual physician moral decision about the duty to care. Hospital or government authority should respond to such decisions without introducing immediate sanction, such as suspension from all clinical duties or termination of licensure, and instead arrange for alternative clinical duties consistent with routine medical care.

Nongenomic glucocorticoid (GC) and serum- and glucocorticoid-inducible kinase 1 (SGK1) signaling regulate ion transport, but CFTR has not been investigated in the intestine. We examined GC, SGK1, and phosphatidylinositol 3-kinase (PI3K) kinase signaling of CFTR ion transport in native intestine and the role of GCs on mRNA, protein, surface expression, and cyclic guanosine monophosphate (cGMP)-elicited diarrhea. Rats were treated with dexamethasone (DEXA; 2 mg/kg ip) or DMSO for 1, 4, and 24 h. Cyclic adenosine monophosphate (cAMP)-activated ion transport was examined in the presence or absence of SGK1 and PI3K inhibitors. Phosphorylation of SGK1, phosphoinositide-dependent kinase 1, and Akt kinases was confirmed by immunoblots using phosphor-specific antibodies. Tissue lysates were analyzed by mass spectrometry. CFTR and SGK1 mRNA were measured by quantitative PCR. Changes in total and surface CFTR protein were determined. The role of GC in cGMP-activated CFTR ion transport was examined. GC synergistically increased CFTR ion transport by SGK1 and PI3K signaling and increased CFTR protein without altering SGK1 or CFTR mRNA. GC induced highest levels of CFTR protein at 4 h that were associated with marked increase in surface CFTR, phosphorylation of the ubiquitin ligase neural precursor cell expressed developmentally downregulated 4-like (Nedd4-2), and 14-3-3ε, supporting their roles in surface retention and stability. Coimmunoprecipitation of CFTR, Nedd4-2, and 14-3-3ε indicated that assembly of this complex is a likely effector of the SGK and Akt pathways. Mass spectrometry identified phosphorylated peptides in relevant proteins. GC-SGK1 potently regulates CFTR in the intestine and is implicated in diarrheal disease. NEW & NOTEWORTHY This is the first study to examine the mechanisms of glucocorticoid, serum- and glucocorticoid-inducible kinase 1, and nongenomic kinase signaling of CFTR in the native intestine. We identified unique and druggable intestine-specific factors of the pathway that are targets for treating stress-induced diarrhea.

Loss-of-function mutations in the nonconventional myosin Vb (Myo5b) result in microvillus inclusion disease (MVID) and massive secretory diarrhea that often begins at birth. Myo5b mutations disrupt the apical recycling endosome (ARE) and membrane traffic, resulting in reduced surface expression of apical membrane proteins. ARE disruption also results in constitutive phosphoinositide-dependent kinase 1 gain of function. In MVID, decreased surface expression of apical anion channels involved in Cl - extrusion, such as cystic fibrosis transmembrane conductance regulator (CFTR), should reduce fluid secretion into the intestinal lumen. But the opposite phenotype is observed. To explain this contradiction and the onset of diarrhea, we hypothesized that signaling effects downstream from Myo5b loss of function synergize with higher levels of glucocorticoids to activate PKA and CFTR. Data from intestinal cell lines, human MVID, and Myo5b KO mouse intestine revealed changes in the subcellular redistribution of PKA activity to the apical pole, increased CFTR phosphorylation, and establishment of apical cAMP gradients in Myo5b-defective cells exposed to physiological levels of glucocorticoids. These cells also displayed net secretory fluid fluxes and transepithelial currents mainly from PKA-dependent Cl - secretion. We conclude that Myo5b defects result in PKA stimulation that activates residual channels on the surface when intestinal epithelia are exposed to glucocorticoids at birth.

Open lumbar discectomy is the gold standard surgical procedure for intervertebral disc herniation but still controversy exit whether limited or aggressive open discectomy provides better outcomes. Retrospectively we evaluate 2380 patients to compare the clinical outcomes, complications and recurrence rate between limited (LD) and aggressive open discectomy (AD). Records of 745 men and 255 women aged 19 to 55 (mean, 38.03±9.1) years for LD and 995 men and 385 women aged 21 to 60 (mean, 43.7±9.3) years for AD were reviewed. Demographic data, surgical data, complications and re-herniation rate were collected and assessment done by Visual analogue score (VAS), Oswestry Disability Index (ODI) and modified Mcnab criteria. The mean follow-up period was 24.5 and 28.8 months respectively. In compare to aggressive discectomy, limited discectomy required significantly less operative time (95 vs. 55 minutes, p<0.001, unpaired 't' test), less used of post-operative analgesic (p<0.05) and better patients' satisfaction (p<0.05). But low back pain, leg pain, recurrence rate, infection, per-operative blood loss and periods of hospitalization were without significant difference. Both groups achieved satisfactory clinical outcomes 85%, 78.62 % respectively. Complications were foot drop (n=2, 5), dural tear (n=7, 14), superficial wound infection (n=7, 17) and discitis (n=19, 37) and reherniation (55, 64) respectively. Limited discectomy is an alternative to the aggressive discectomy. Both groups showed satisfactory outcome but in limited discectomy group shown better satisfaction in relation to aggressive discectomy.

Spine injuries, a common component in Polytrauma are usually affects the young people and is a major cause of morbidity and poses a significant health care expenditure and considerable threats to survival and quality of life. We retrospectively assess the demographics, incidence, mode of trauma, associated spine injuries, complications, neurological improvement and mortality. Records of total 1695 admitted patients, spinal injuries were 262 patients. Among them 30(11.45%) patients were associated with Polytrauma victims. Eleven patients (36.67%) were admitted through Ortho emergency dept, 14(46.67%) patients through Intensive care unit (ICU), 5(16.66%) patients through other department (CVS, Urology). Most (56%) of the patients were young in the age range of 16 to 40 years. Cervical spines were most commonly (44%) affected followed by lumbar (31%), thoracic (13%), thoraco-lumbar (9%) and Cervico-thoracic (3%) spines. Road traffic accident was the common cause (80%). Twelve patients (40%) had problems at various steps of management and maximum problems occur in step III. Nineteen patients (63.33%) management needs co-ordination between various specialties. Significant number of patients (76.67%) required operative treatment (p<0.05) and 13.33% were managed conservatively. Mortality rate (10%) was insignificant (p>0.05%). Of these patients, 73.33% had shown neurological improvement of at least one ASIA grade. The treatment of spinal injury in polytrauma patient should follow the principle of Advanced Trauma Life Support (ATLS). Once life and limb-threatening injuries have been identified and addressed, suspected spinal cord injury patients should be immobilized as early as possible to reduced the secondary injury, improve motor and sensory function as well as reduced the extend of permanent paralysis.

The treatment of unstable thoracolumbar junction burst fractures remains a controversial issue. We evaluate the efficacy of short segment (SS) compared with that of long-segment (LS) stabilization in terms of clinical and the radiological outcomes. Records of 88 patients with thoracolumbar burst fracture underwent posterior pedicle screw fixation from January 2004 to December 2015, studied retrospectively. These patients were divided into two groups: SS and the LS-group. Clinical parameters: back pain, disability, neurological deficit and radiologic parameters: Cobb angle, sagittal index, the kyphotic deformation of vertebral body, vertebral height and canal compromise were measured before surgery and immediately after surgery and at 3, 6 and 12 months postoperatively. Overall outcomes were evaluated using the modified Mcnab criteria at the last follow-up. Chi-squared test and paired-t test were used for statistical analysis using SPSS. There were 36 and 52 patients in the SS and LS- group, respectively. The mean age of the patients was 30.6±8.4 and 33.4±8.4 years and the mean follow-up period was 24.5 and 16.8 months in SS and LS-group respectively. In the SS-group, the fractured vertebral body level was L1, T12, L2, T11 and T10 in 15, 10, 6, 3 and 2 cases and LS- group, the fractured vertebral body level was L1, T12, L2, T11 and T10 in 22, 17, 5, 5 and 3 cases, respectively. Both groups achieved satisfactory clinical outcomes according to the modified Mcnab criteria. In the SS-group, 8(22.22%), 21(58.33%) and 7(19.44%) cases were considered to have excellent, good and fair outcome and LS-group, 18(34.61%), 25(48.08%), 6(11.54%) and 3(5.77%) cases were considered to have excellent, good, fair, and poor outcome, respectively. Short-segment pedicle screw fixation including the fractured vertebral body might be as effective as long-segment pedicle screw fixation for the treatment of unstable thoracolumbar junction burst fracture.

To review outcome of 25 patients who underwent open-door cervical laminoplasty for multilevel cervical spondylotic myelopathy (MCSM) and ossification of the posterior longitudinal ligament (OPLL) using titanium reconstruction miniplate and screws. Records of 18 men and 7 women aged 35 to 78 (mean, 62.6) years were reviewed retrospectively from October 2009 and October 2014 at Bangabandhu Sheikh Mujib Medical University (BSMMU) and in our private settings, Dhaka, Bangladesh. Four patients had 5 levels (C3-C7), 21 patients had 4 levels (C3-C6) decompression and 3 patients (12%) performed foraminotomies. A total of 104 laminae were opened, all of them were fixed with a titanium reconstruction miniplates. In 21 patients, a 20-hole titanium miniplate bent to the contour of a lamina was used and fixed into 4 laminae and 4 patients fixed in 5 laminae levels. In most patients, screw fixation was unicortical and no spacer or bone graft was used. Demographic and surgical data were collected and clinical outcomes were assessed with neck pain score, neck disability index and Nurick's grading. Outcome analysis was done using Odom's criteria. The mean follow-up duration was 1.8 (range, 1-5) years. Diagnoses were MCSM (n=20), OPLL (n=5). Mean estimated blood loss (EBL) was 120ml (range: 50-200), mean surgery time was 153 min (range: 75-240). Following Nurick's grading, 23 patients (92%) improved, 2 (08%) had the same Nurick grade. No intraoperative complications were noted and average hospital stay was 6.12 days (range: 5 to 9). Significance improvements in overall NDI scores occurred at 1 year follow up (p<0.002). Radiographic evaluation showed an increase in the mean sagittal diameter from 13.3mm at pretreatment to 19.4mm post surgery. Two patients developed transient C5 palsy. Open-door Laminoplasty technique is safe, easy and achieves a good canal expansion and neurological recovery and can be used as an alternative treatment for cases of MCSM and OPLL patients without instability.

The transmembrane receptor guanylyl cyclase-C (GC-C), expressed on enterocytes along the intestine, is the molecular target of the GC-C agonist peptide linaclotide, an FDA-approved drug for treatment of adult patients with Irritable Bowel Syndrome with Constipation and Chronic Idiopathic Constipation. Polarized human colonic intestinal cells (T84, CaCo-2BBe) rat and human intestinal tissues were employed to examine cellular signaling and cystic fibrosis transmembrane conductance regulator (CFTR)-trafficking pathways activated by linaclotide using confocal microscopy, in vivo surface biotinylation, and protein kinase-II (PKG-II) activity assays. Expression and activity of GC-C/cGMP pathway components were determined by PCR, western blot, and cGMP assays. Fluid secretion as a marker of CFTR cell surface translocation was determined using in vivo rat intestinal loops. Linaclotide treatment (30 min) induced robust fluid secretion and translocation of CFTR from subapical compartments to the cell surface in rat intestinal loops. Similarly, linaclotide treatment (30 min) of T84 and CaCo-2BBe cells increased cell surface CFTR levels. Linaclotide-induced activation of the GC-C/cGMP/PKGII signaling pathway resulted in elevated intracellular cGMP and pVASP ser239 phosphorylation. Inhibition or silencing of PKGII significantly attenuated linaclotide-induced CFTR trafficking to the apical membrane. Inhibition of protein kinase-A (PKA) also attenuated linaclotide-induced CFTR cell surface trafficking, implying cGMP-dependent cross-activation of PKA pathway. Together, these findings support linaclotide-induced activation of the GC-C/cGMP/PKG-II/CFTR pathway as the major pathway of linaclotide-mediated intestinal fluid secretion, and that linaclotide-dependent CFTR activation and recruitment/trafficking of CFTR from subapical vesicles to the cell surface is an important step in this process., (© 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

Loss of function mutations in the actin motor myosin Vb (Myo5b) lead to microvillus inclusion disease (MVID) and death in newborns and children. MVID results in secretory diarrhea, brush border (BB) defects, villus atrophy, and microvillus inclusions (MVIs) in enterocytes. How loss of Myo5b results in increased stool loss of chloride (Cl(-)) and sodium (Na(+)) is unknown. The present study used Myo5b loss-of-function human MVID intestine, polarized intestinal cell models of secretory crypt (T84) and villus resembling (CaCo2BBe, C2BBe) enterocytes lacking Myo5b in conjunction with immunofluorescence confocal stimulated emission depletion (gSTED) imaging, immunohistochemical staining, transmission electron microscopy, shRNA silencing, immunoblots, and electrophysiological approaches to examine the distribution, expression, and function of the major BB ion transporters NHE3 (Na(+)), CFTR (Cl(-)), and SLC26A3 (DRA) (Cl(-)/HCO3 (-)) that control intestinal fluid transport. We hypothesized that enterocyte maturation defects lead villus atrophy with immature secretory cryptlike enterocytes in the MVID epithelium. We investigated the role of Myo5b in enterocyte maturation. NHE3 and DRA localization and function were markedly reduced on the BB membrane of human MVID enterocytes and Myo5bKD C2BBe cells, while CFTR localization was preserved. Forskolin-stimulated CFTR ion transport in Myo5bKD T84 cells resembled that of control. Loss of Myo5b led to YAP1 nuclear retention, retarded enterocyte maturation, and a cryptlike phenotype. We conclude that preservation of functional CFTR in immature enterocytes, reduced functional expression of NHE3, and DRA contribute to Cl(-) and Na(+) stool loss in MVID diarrhea.

Results of 63 surgically treated intradural spinal tumors between the period of October 2003 and December 2014 at Bangabandhu Sheikh Mujib Medical University (BSMMU) and in our private settings, Dhaka, were analyzed retrospectively. There were 33 males, 30 females with an average age of 52.4 years (13-70 years) and followed up for at least a year. The preoperative symptom with duration, tumors location and intradural space occupancy and the histopathological diagnosis were analyzed. Pain was evaluated by the visual analogue scale (VAS) and the neurologic function was assessed by Nurick's grade. The tumors were located as, thoracic (n=32, 50.79%), lumbar (n=16, 25.39%), cervical (n=05, 07.93%), and junctional (n=10, 15.87%, CervicoThoracic-01, Thoracolumbar-09). The histopathological diagnosis included schwannoma (n=30, 47.7%), meningiomas (n=14, 22.3%), neurofibroma, arachnoid cyst and myxopapillary ependymoma (n=03, 04.76%) each and paraganglioma (n=01, 01.59%). Among the intramedullary tumors, ependymoma (n=03, 04.76%), astrocytoma and epidermoid cyst (n=02, 03.17%), haemangioblastoma, paraganglioma and cavernous haemangioma (n=01, 01.59%) each. The VAS score was reduced in all cases from 8.0±1.2 to 1.2±0.8 (p<0.003) and the Nurick's grade was improved in all cases from 3.0±1.3 to 1.0±0.0 (p<0.005). The preoperative neurological deficit improved within 8 postoperative weeks in most cases and within 1 postoperative year in all cases. Complications included cerebrospinal fluid leakage, parasthesia and further neurological deterioration (Astrocytoma) (n=02, 03.17%) and dependant bedsore and recurrence (Ependymoma) (n=01, 01.59%). Aggressive surgical excision potentially minimizes neurologic morbidity and improved outcome except intramedullary tumors where initial treatment consists of maximum safe surgical resection or biopsy.

Out of wide range of surgical techniques direct repair techniques are emphasized to avoid fusion related complications in pars defects. To assess the clinical, functional and radiological outcome of direct operative repair of pars defects by intra-laminar screws and bone graft, this retrospective study was done in Bangabandhu Sheikh Mujib Medical University and in our private settings, within the period of July 2005 to December 2012. Records of 12 patients (age range, 21-35 years) with symptomatic pars defect, 07 men and 05 women (mean 28 years) who underwent direct pars repair with intralaminar screws and bone graft were reviewed. The surgical time, intra-operative blood loss, post operative hospital stay and time to achieve union was recorded. Self evaluated back pain [using Visual Analogue Score (VAS)] and disability [using Oswestry disability (ODI) questionnaire] was analyzed. Clinical outcome was assessed [using Modified Prolo Scale], Radiological fusion (using Shin criteria), restoration of total lumbar lordosis (TLL) and overall functional outcome [using Odom's Criteria] was calculated. Chi-squared test and paired-t test were used for statistical analysis using SPSS. The VAS, ODI and clinical outcome had significant (p<0.05) improvement as had the radiological fusion and TLL. Overall satisfactory outcome was achieved in 91.67% cases. Despite of no intra-operative or post-operative complications, pseudarthrosis developed in 01 case which could be managed conservatively. Direct repair of spondylitic defect with intra-laminar screws and bonegraft is satisfactory in properly selected cases.

The present study was carried out with the aims to diagnose abdominal masses by FNAC with the help of ultrasonography guidance and to determine the diagnostic accuracy of FNAC. One hundred consecutive patients were studied during the period from January 2005 to December 2005. Histopathological examination was done to correlate with the cytologic diagnosis. The results of comparative study of USG-guided FNAC and histopathology were significant (P value was <0.001). In USG-guided FNAC, it was found that 64 were malignant tumors, 5 were benign tumors, 28 were inflammatory and 3 were inadequate material. Histopathology of 3 inadequate materials showed 1 was adenoma and 2 were leiomyoma. As a whole test results of USG-guided FNAC were sensitivity 95.52%, specificity 100%, positive predictive value 100%, negative predictive value 91.67% and accuracy 97%. USG-guided FNAC has been proved to be a rapid, reliable and cost-effective diagnostic method.

"Upper" lumbar disc herniations (LDH) are different from the "lower" and possess increased chance of neural compromise and cauda equina syndrome that necessitates operative management despite of contradictory surgical outcome. We underwent the study to assess the clinical and functional outcome of symptomatic upper LDH surgery from July 2003 to June 2012 in BSMMU, Dhaka, Bangladesh. The records of 123 patients (age range, 30-69 years), 56 men and 67 women (mean 52 years) having upper lumbar discectomy were reviewed. The surgical time, intra-operative blood loss, self evaluated back pain and thigh and/or groin pain status [using Visual Analogue Score (VAS)] and the disability status [using Oswestry disability (ODI) questionnaire] was analyzed. Radiological stability (using Posner's criteria), functional outcome [using Japanese Orthopaedic Association (JOA) Score] and overall outcome (using MacNab`s criteria), was calculated. Chi-squared test and z-test using SPSS revealed mean operative time and mean blood loss had no significant (p>0.05) difference. Pain, sensory, motor and reflex status as well as VAS, ODI and all the components of JOA questionnaire had significant (p<0.05) improvement. In spite of intra-operative complications in 20.32% cases, overall satisfactory outcome was achieved in 83.74% cases. The postoperative complications (08.13%) could be managed conservatively. However, carefully decided surgical alternatives resulted in satisfactory clinical and functional outcome in upper LDH surgery.

Isthmic spondylolisthesis (IS) is the most common spondylolytic disorders and one of the most common causes of low back pain and sciatica in adolescents and adults. Although the initial management is conservative, surgery is often the ultimate solution. Interbody fusion has been found superior and replaced the gold standard postero-lateral fusion. Transforaminal Lumbar Interbody Fusion (TLIF) has been associated with fewer complications and has become the choice of surgery. This study was done to evaluate the clinical, radiological and functional outcome of TLIF in Low Grade Isthmic Spondylolisthesis (LGIS). The clinical records of 46 consecutive patients within the age range of 31 to 60 years, who had symptomatic unstable Low Grade Isthmic Spondylolisthesis (LGIS) with or without unilateral radiculopathy in Bangabandhu Sheik Mujib Medical University (BSMMU) and private settings, from April 2007 to March 2012 were reviewed with 2 year completed follow-up. Patients were evaluated for pain by Visual Analogue Score (VAS), Disability by Oswestry Disability Index (ODI), radiological fusion by Brantigan and Steffee criteria, reduction of listhesis by Taillard's method and the overall functional outcome by the Macnab's criteria. Pain (Low back and leg), disability, neurological status had highly significant (p<0.001, paired t test) improvement. Forty two (91.30%) cases achieved satisfactory radiological fusion with overall 30% reduction of slip. Satisfactory outcome was reached in 45(97.83%) cases. Transforaminal Lumbar Interbody Fusion results in significant improvement of clinical, radiological and functional debility of symptomatic LGIS in adults.

Background and Aims: During fibrosis hepatic stellate cells (HSC) undergo activation, proliferation, and senescence but the regulation of these important processes is poorly understood. The adenosine A2A receptor (A2A) is known to be present on HSC, and its activation results in liver fibrosis. In this study, we tested if A2A has a role in the regulation of HSC proliferation, apoptosis, senescence, and the relevant molecular mechanism., Methods: The ability of adenosine to regulate p53 and Rb protein levels, proliferation, apoptosis and senescence was tested in the human HSC cell line LX-2 and rat primary HSC., Results: Adenosine receptor activation down-regulates p53 and Rb protein levels, increases BrdU incorporation and increases cell survival in LX-2 cells and in primary rat HSC. These effects of NECA were reproduced by an adenosine A2A receptor specific agonist (CGS21680) and blocked by a specific antagonist (ZM241385). By day twenty-one of culture primary rat HSC entered senescence and expressed β-gal which was significantly inhibited by NECA. Furthermore, NECA induced down regulation of p53 and Rb and Rac1, and decreased phosphorylation of p44-42 MAP Kinase in LX-2 cells and primary rat HSC. These effects were reproduced by the cAMP analog 8-Bromo-cAMP, and the adenylyl cyclase activator forskolin, and were blocked by PKA inhibitors., Conclusions: These results demonstrate that A2A receptor regulates a number of HSC fate decisions and induces greater HSC proliferation, reduces apoptosis and senescence by decreasing p53 and Rb through cAMP-PKA/Rac1/p38 MAPK pathway. This provides a mechanism for adenosine induced HSC regulation and liver fibrosis.

This prospective interventional study carried out at Bangabandhu Sheikh Mujib Medical University and a private hospital in Dhaka, Bangladesh during the period from October 2003 to September 2011. Surgical treatment of degenerative disc disease (DDD) should aim to re-expand the interbody space and stabilize until fusion is complete. The present study conducted to find out the efficacy of using interbody fusion device (Cage) to achieve interbody space re-expansion and fusion in surgical management of DDD. We have performed the interventional study on 53 patients, 42 female and 11 male, with age between 40 to 67 years. All the patients were followed up for 36 to 60 months (average 48 months). Forty seven patients were with spondylolisthesis and 06 with desiccated disc. All subjects were evaluated with regard to immediate and long term complications, radiological fusion and interbody space re-expansion and maintenance. The clinical outcome (pain and disability) was scored by standard pre and postoperative questionnaires. Intrusion, extrusion and migration of the interbody fusion cage were also assessed. Forty seven patients were considered to have satisfactory outcome in at least 36 months follow up. Pseudoarthrosis developed in 04 cases and 06 patients developed complications. In this series posterior lumbar interbody fusion (PLIF) with interbody cage and instrumentation in DDD showed significant fusion rate and maintenance of interbody space. Satisfactory outcome observed in 88.68% cases.

Lumbar disc herniation (LDH) is a disabling problem. This retrospective case control study was done to evaluate the possible relevance of physical work load with Lumbar Disc Herniation. We have performed this study in the Spinal Surgery Unit of Department of Orthopaedic Surgery at BSMMU, Dhaka from July 2007 to June 2010 where 200 cases with Lumbar Disc Herniation and 200 control subjects matched by age, gender and area of residence were taken and analyzed. Chi-square test was computed for sex, area of residence, type of physical work and effort at work, whereas Odds ratio was computed for physical work load, stress at work and daily working period. The highest odds ratio (OR) was with the physical work load (OR: 03.48, CI: 01.84-06.59), hard work (OR: 03.14, CI: 01.74-05.65) and working period of >8 hours (OR: 01.34, CI: 0.75-02.38). Odds ratio for heavy load carrying at work was 03.48 and less job satisfaction or stress at work was 02.45. There was a statistically significant positive association between cumulative exposure of physical work load and lumbar disc herniation indicating an increased occurrence of herniation in heavy physical work load and occupation requiring harder efforts.

Resveratrol, a constituent of red wine, and γ-tocotrienol, a constituent of palm oil are important for cardioprotection. Although microRNAs are known regulators for genes involved in cardiac remodelling, the regulatory pathway involving microRNA has not been studied so far. We explored the cardioprotection by resveratrol, longevinex and γ-tocotrienol in ischaemia/reperfusion(I/R) model of rat and determined miRNA profile from isolated RNA. Systemic analyses of miRNA array and theirs targets were determined using a number of computational approaches. Resveratrol and γ-tocotrienol, either alone or in combination, modulated the expression pattern of miRNAs close to the control level based on PCA analyses. Differential expression was observed in over 75 miRNAs, some of them, such as miR-21 and miR-20b (anti-angiogenic) were previously implicated in cardiac remodelling. The target genes for the highest differentially expressed miRNA include genes of various molecular functions such as TGFβ1-Smad3 signalling pathway, inflammation and their transcription factors, which may play key role in reducing I/R injury. Administration of antagomiR-20 attenuated I/R induced vascular endothelial growth factor and HIF1α level. All the interventions treated for 3 weeks lead to significant cardioprotection against ischaemia/reperfusion injury. A unique signature of miRNA profile is observed in control heart pretreated with resveratrol or γ-tocotrienol. We have determined specific group of miRNA in heart that have altered during IR injuries. Most of those altered microRNA expressions modulated close to their basal level in resveratrol or longevinex treated I/R rat. Interestingly, resveratrol and γ-tocotrienol resulted in synergestic action., (© 2012 The Authors Journal of Cellular and Molecular Medicine © 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.)

Objectives: Endotoxin triggers a reorganization of the energy metabolic pathway, including the promotion of fatty acid utilization to adapt to a high energy demand during endotoxemia. However, the factors responsible for the metabolic adaptation and characteristic pathologies resulting from defective utilization fatty acids during endotoxin response have not been fully clarified. The thioredoxin binding protein-2 (TBP-2) knockout (TBP-2) mouse is an animal model of fatty acid oxidation disorder. The aim of this study was to determine whether and how TBP-2 is involved in metabolic regulation in a lipopolysaccharide (LPS)-induced endotoxemia model in mice., Design: Prospective animal trial., Setting: Research laboratory., Subjects: TBP-2 and wild control mice., Intervention: TBP-2 and wild control mice were intraperitoneally injected with LPS. Mortality, serum levels of markers of hepatorenal injuries, cytokines, insulin, glucose and lipid derivatives, and the hepatic signaling pathway regulating gluconeogenesis were investigated., Measurements and Main Results: Following the administration of LPS, TBP-2 mice showed a predisposition for death without any significant elevation of inflammatory cytokines, compared to the wild mice. LPS-challenged TBP-2 mice showed fat deposition in the liver and kidney, organ injuries, glycogen depletion, and elevation of serum lipid derivatives such as free fatty acids, triglyceride and cholesterol. Hyperinsulinemia and hypoglycemia were observed in TBP-2 mice after LPS injection. Death due to the LPS administration was prevented by supplementation of glucose. Phosphorylation of Akt and FoxO1, an inhibitory pathway of gluconeogenesis in the liver of LPS-challenged TBP-2 mice was demonstrated, suggesting the enhancement of insulin signaling., Conclusions: TBP-2 is involved in metabolic control during LPS-induced endotoxemia. After the LPS challenge, TBP-2 mice showed several characteristic aspects, such as hepatorenal injuries, and dysregulation of the lipid and glucose metabolisms. Furthermore, hypoglycemia promoted by hyperinsulinemia may be a critical risk factor for mortality in circumstances in which fatty acid utilization is impaired during endotoxemia.

This study compared two dietary phytochemicals, grape-derived resveratrol and palm oil-derived γ-tocotrienol, either alone or in combination, on the contribution of autophagy in cardioprotection during ischaemia and reperfusion. Sprague-Dawley rats weighing between 250 and 300 g were randomly assigned to one of the following groups: vehicle, ischaemia/reperfusion (I/R), resveratrol + I/R, γ-tocotrienol + I/R, resveratrol +γ-tocotrienol + I/R. For resveratrol treatments, the rats were gavaged with resveratrol (2.5 mg/kg) for 15 days while for γ-tocotrienol experiments the rats were gavaged with γ-tocotrienol (0.3 mg/kg) for 30 days. For the combined resveratrol +γ-tocotrienol experiments, the rats were gavaged with γ-tocotrienol for 15 days, and then gavaging continued with resveratrol along with γ-tocotrienol for a further period of 15 days. After 30 days, isolated perfused hearts were subjected to 30 min. of global ischaemia followed by 2 hrs of reperfusion. Our results showed for the first time that at least in part, the cardioprotection (evidenced from the ventricular performance, myocardial infarct size and cardiomyocyte apoptosis) with resveratrol and γ-toctrienol was achieved by their abilities to induce autophagy. Most importantly, resveratrol and γ-tocotrienol acted synergistically providing greater degree of cardioprotection simultaneously generating greater amount of survival signal through the activation of Akt-Bcl-2 survival pathway. Autophagy was accompanied by the activation of Beclin and LC3-II as well as mTOR signalling, which were inhibited by either 3-methyl adenine (3-MA) or Wortmannin. The autophagy was confirmed from the results of transmission electron microscopy and light microscopy as well as with confocal microscopy. It is tempting to speculate that during ischaemia and reperfusion autophagy along with enhanced survival signals helps to recover the cells from injury., (© 2009 The Authors Journal compilation © 2010 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.)

Aims: On the basis of our previous reports that cardioprotection induced by ischaemic preconditioning induces autophagy and that resveratrol, a polyphenolic antioxidant present in grapes and red wine induces preconditioning-like effects, we sought to determine if resveratrol could induce autophagy., Methods and Results: Resveratrol at lower doses (0.1 and 1 microM in H9c2 cardiac myoblast cells and 2.5 mg/kg/day in rats) induced cardiac autophagy shown by enhanced formation of autophagosomes and its component LC3-II after hypoxia-reoxygenation or ischaemia-reperfusion. The autophagy was attenuated with the higher dose of resveratrol. The induction of autophagy was correlated with enhanced cell survival and decreased apoptosis. Treatment with rapamycin (100 nM), a known inducer of autophagy, did not further increase autophagy compared with resveratrol alone. Autophagic inhibitors, wortmannin (2 microM) and 3-methyladenine (10 mM), significantly attenuated the resveratrol-induced autophagy and induced cell death. The activation of mammalian target of rapamycin (mTOR) was differentially regulated by low-dose resveratrol, i.e. the phosphorylation of mTOR at serine 2448 was inhibited, whereas the phosphorylation of mTOR at serine 2481 was increased, which was attenuated with a higher dose of resveratrol. Although resveratrol attenuated the activation of mTOR complex 1, low-dose resveratrol significantly induced the expression of Rictor, a component of mTOR complex 2, and activated its downstream survival kinase Akt (Ser 473). Resveratrol-induced Rictor was found to bind with mTOR. Furthermore, treatment with Rictor siRNA attenuated the resveratrol-induced autophagy., Conclusion: Our results indicate that at lower dose, resveratrol-mediated cell survival is, in part, mediated through the induction of autophagy involving the mTOR-Rictor survival pathway.

CLP-1, the mouse homologue of human Hexim1 protein, exerts inhibitory control on transcriptional elongation factor-b of RNA transcript elongation. Previously, we have demonstrated that downregulation of cardiac lineage protein-1 (CLP-1) in CLP-1(+/-) heterozygous mice affords cardioprotection against ischemia-reperfusion injury. Our current study results show that the improvement in cardiac function in CLP-1(+/-) mice after ischemia-reperfusion injury is achieved through the potentiation of redox signaling and their molecular targets including redox effector factor-1, nuclear factor erythroid 2-related factor, and NADPH oxidase 4 and the active usage of thioredoxin-1, thioredoxin-2, glutaredoxin-1 and glutaredoxin-2. Our results suggest that drugs designed to down regulate CLP-1 could confer cardioprotection through the potentiation of redox cycling.

Reactive oxygen species (ROS) are the key mediators of pathogenesis in cardiovascular diseases. Members of the thioredoxin superfamily take an active part in scavenging reactive oxygen species, thus playing an essential role in maintaining the intracellular redox status. The alteration in the expression levels of thioredoxin family members and related molecules constitute effective biomarkers in various diseases, including cardiovascular complications that involve oxidative stress. Thioredoxin, glutaredoxin, peroxiredoxin, and glutathione peroxidase, along with their isoforms, are involved in interaction with the members of metabolic and signaling pathways, thus making them attractive targets for clinical intervention. Studies with cells and transgenic animals have supported this notion and raised the hope for possible gene therapy as modern genetic medicine. Of all the molecules, thioredoxins, glutaredoxins, and peroxiredoxins are emphasized, because a growing body of evidence reveals their essential and regulatory role in several steps of redox regulation. In this review, we discuss some pertinent observations regarding their distribution, structure, functions, and interactions with the several survival- and death-signaling pathways, especially in the myocardium.

In nonalcoholic fatty liver disease, oxidative stress is believed to play a crucial role as a second-hit for the progression of simple steatosis to steatohepatitis. Thioredoxin (TRX) is a potent antioxidant molecule that exerts anti-apoptotic and anti-inflammatory functions. TRX-binding protein-2 (TBP-2) is an endogenous negative regulator of TRX. Deficiency of TBP-2 in mice causes hyperlipidemia, hepatic steatosis, hypoglycemia, and bleeding tendency, resembling Reye syndrome in a fasting/glucose-deficient state. The aim of this study was to investigate the role of TBP-2 in the development of nonalcoholic steatohepatitis (NASH). TBP-2-deficient (TBP-2(-/-)) and wild-type (WT) mice were fed either a normal or methionine-choline-deficient (MCD) diet for up to 10 weeks. Compared with WT mice, TBP-2(-/-) mice showed severe simple steatosis rather than steatohepatitis. However, oxidative stress determined by lipid peroxidation and DNA damage, neutrophil infiltration, and hepatic fibrosis were attenuated in TBP-2(-/-) mice. PCR analysis showed the expressions of fibrosis-inducing and inflammatory cytokine-related genes were less in TBP-2(-/-) mice. Moreover, leptin, SREBP1c, PPARgamma, and adipogenesis-lipogenesis-related genes were upregulated in TBP-2(-/-) mice. These results strongly suggested that TBP-2 might be involved in pathogenesis of NASH in WT mice, and inhibitors of TBP-2 could be useful in the prevention or treatment of NASH.

Thioredoxin (TRX) is a 12-kDa protein with redox-active dithiol in the active site -Cys-Gly-Pro-Cys- and constitutes a major thiol reducing system. TRX protects cells from stress-induced damage through antioxidative, antiapoptotic, and anti-inflammatory effect. In animal models, thioacetamide (TAA)-induced acute hepatitis and TAA-induced liver fibrosis was attenuated in TRX transgenic (TRXTG) mice. Plasma level of TRX is a good marker for hepatitis and nonalcoholic steatohepatitis (NASH) in human patients. Recently, we identified TRX binding protein 2 (TBP2) in a yeast two-hybrid screening. TBP2 regulates both the expression and reducing activity of TRX as well as cell growth. TBP2 knockout (TBP2KO) mice showed disorder in lipid metabolism. TBP2 plays a multiple role on cell growth and lipid and glucose metabolism. Thus, TRX and TBP2 play important roles in the pathophysiology of liver diseases, including NASH, indicating that ratio of TRX and TBP2 expression could be a novel marker of liver diseases like NASH.

Indomethacin is one of non-steroidal anti-inflammatory drugs that are commonly used clinically and often cause gastric mucosal injury as a side effect. Generation of reactive oxygen species (ROS) and activation of apoptotic signaling are involved in the pathogenesis of indomethacin-induced gastric mucosal injury. Thioredoxin-1 (Trx-1) is a small redox-active protein with anti-oxidative activity and redox-regulating functions. The aim of this study was to investigate the protective effect of Trx-1 against indomethacin-induced gastric mucosal injury. Trx-1 transgenic mice displayed less gastric mucosal damage than wild type (WT) C57BL/6 mice after intraperitoneal administration of indomethacin. Administration of recombinant human Trx-1 (rhTrx-1) or transfection of the Trx-1 gene reduced indomethacin-induced cytotoxicity in rat gastric epithelial RGM-1 cells. Pretreatment with rhTrx-1 suppressed indomethacininduced ROS production and downregulation of phosphorylated Akt in RGM-1 cells. Survivin, a member of inhibitors of apoptosis proteins family, was downregulated by indomethacin, which was suppressed in Trx-1 transgenic mice or by administration of rhTrx-1 in RGM-1 cells. Trx-1 inhibits indomethacin-induced apoptotic signaling and gastric ulcer formation, suggesting that it may have a preventive and therapeutic potential against indomethacin-induced gastric injury.

The transition from interleukin-2 (IL-2)-dependent to IL-2-independent growth is considered one of the key steps in the transformation of human T-cell leukemia virus type-I (HTLV-I)-infected T cells. The expression of thioredoxin-binding protein-2 (TBP-2) is lost during the transition of HTLV-I-infected T-cell lines. Here, we analysed the mechanism of loss of TBP-2 expression and the role of TBP-2 in IL-2-dependent growth in the in vitro model to investigate multistep transformation of HTLV-I. CpGs in the TBP-2 gene are methylated in IL-2-independent but not in IL-2-dependent cells. Sequential treatment with 5-aza-2'-deoxycytidine and a histone deacetylase inhibitor augmented histone acetylation and TBP-2 expression, suggesting that loss of TBP-2 expression is due to DNA methylation and histone deacetylation. In IL-2-dependent cells, a basal level of TBP-2 expression was maintained by IL-2 associated with cellular growth, whereas TBP-2 expression was upregulated on deprivation of IL-2 associated with growth suppression. Overexpression of TBP-2 in IL-2-independent cells suppressed the growth and partially restored responsiveness to IL-2. Knockdown of TBP-2 caused the IL-2-dependent cells to show partial growth without IL-2. These results suggested that epigenetic silencing of the TBP-2 gene results in a loss of responsiveness to IL-2, contributing to uncontrolled IL-2-independent growth in HTLV-I-infected T-cell lines.

Thioredoxin (TRX) binding protein-2 (TBP-2), a negative regulator of TRX, is involved in intracellular redox regulation and cellular growth. The expression of TBP-2 is frequently lost in tumor cell lines and tissues, whereas the ectopic expression of TBP-2 suppresses cellular proliferation along with cell cycle arrest at the G1 phase. TBP-2 was also reported to be a cellular senescence-associated gene. Besides the retardation of cellular growth, the reduction of white adipose, and alteration of the energy pathway are involved in several features of the aging process. We have generated TBP-2 genetically modified mice and found that TBP-2 is closely linked to lipid metabolism. Indeed, TBP-2 has been suggesting to be related to familial combined hyperlipidemia analyzed by a spontaneous mutant mouse strain. As lipid metabolism is one of the most primitive sources of energy production, we discussed the possible roles of TBP-2 in the regulation of energy utilization connected to the aging process.

To investigate the cellular basis of the action of thyroid hormone on hair follicles, we studied the immunohistochemical localization of thyroid hormone receptors (TRs) in human scalp skin using a mouse monoclonal antibody, TR alpha 1 (C4) against TRs. Immunoreactive TRs were detected in the nuclei of the outer root sheath cells (ORSCs), dermal papilla cells (DPCs), fibrous sheath cells of hair follicles, hair arrector pili muscle cells and sebaceous gland cells. However, nuclei of hair matrix cells were not clearly stained with TR alpha 1 (C4). The epidermis showed positive nuclear staining by the antibody. Ductal and secretory portions of eccrine sweat glands were also stained with the antibody as we had expected. In the dermis, almost all the cell components including fibroblasts, vascular endothelial and smooth muscle cells, and Schwann cells were positively stained. Immunofluorescence also showed TRs expression in cultured ORSCs, DPCs, epidermal keratinocytes and dermal fibroblasts. L-triiodothyronine stimulated the proliferation and/or metabolism of all these four types of cells significantly, although there was variation at the rate of stimulation. Whereas, structurally similar, but metabolically inactive analog, reverse T3 had no effect. These results demonstrate the presence of thyroid hormone nuclear receptors in human hair follicles. Furthermore, the presence of TRs in different cell types in the skin suggests numerous direct effects of thyroid hormone on this target tissue.