Publications by authors named "Hussain Mansoor"

Article Synopsis
  • - Urolithin A (UA), a compound derived from ellagic acid, shows promise in improving cognitive functions and countering amyloid beta and tau pathologies in Alzheimer's disease (AD) models in mice.
  • - Long-term UA treatment enhances mitophagy by boosting lysosomal functions and normalizing lysosomal cathepsins, especially cathepsin Z, which is crucial for its therapeutic effects on AD.
  • - The findings underscore the significance of lysosomal dysfunction in AD and suggest UA as a potential treatment by influencing immune responses and AD-related pathways.
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Heart failure with preserved ejection fraction (HFpEF) afflicts over half of all patients with heart failure and is a debilitating and fatal syndrome affecting postmenopausal women more than any other demographic. This bias toward older females calls into question the significance of menopause in the development of HFpEF, but this question has not been probed in detail. In this study, we report the first investigation into the impact of ovary-intact menopause in the context of HFpEF.

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  • Mutations in RECQL4 cause Rothmund-Thomson syndrome (RTS), which leads to mitochondrial dysfunction, premature aging, and genomic instability, but the exact mechanisms are not fully understood.
  • RECQL4 is modified by MITOL, a mitochondrial E3 ligase, which prevents its entry into mitochondria, impairing mitochondrial DNA replication.
  • In RTS patient mutants, RECQL4 is hyperubiquitylated, forming aggregates and hindering mtDNA replication, but reducing MITOL levels allows RECQL4 to enter mitochondria and improve replication, suggesting a potential therapeutic approach.
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  • * The specific type of DNA damage, 8-oxoG, is repaired by OGG1, an enzyme found in the nucleus and mitochondria, playing a crucial role in maintaining mitochondrial function and reducing inflammation.
  • * Enhanced expression of mitochondria-targeted OGG1 (mtOGG1) in transgenic mice shows promise in reversing age-related inflammation and improving mitochondrial functions, with notable differences in response between male and female mice.
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  • RecQ helicases are crucial for maintaining DNA stability and are linked to various diseases when dysfunctional, such as cancer and neurodegeneration.
  • This study examined the effects of ionizing radiation (IR) on mice lacking specific RecQ proteins (RecQ1, WRN, and RecQ4), revealing abnormal behavior patterns, including social and depressive-like issues.
  • Transcriptomic and metabolomic analyses indicated significant changes in neurological pathways and increased DNA damage responses in these mice, highlighting potential therapeutic targets like the Aldob and Nox4 genes.
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Background: Alopecia Areata (AA) is found to be the most prevalent autoimmune disorder amongst the general population. It was observed that AA patients are at a significantly higher risk of developing obstructive sleep apnea and non-apneic insomnia than patients without AA. On the contrary, patients with identified sleep disorders were found to be more prone to developing AA as compared to the patients without sleep disorders.

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Article Synopsis
  • - PARPs are crucial for DNA damage repair, but while we know about nuclear PARP functions, the role of mitochondrial PARP (mtPARP) remains largely unexplored and controversial.
  • - This study provides evidence of PARP1 and poly ADP-ribosylation (PARylation) occurring in purified mitochondria, where adding NAD stimulates this process.
  • - Results indicate that PARP1 not only participates in mitochondrial PARylation but also plays a role in regulating the transcription of mitochondrial DNA (mtDNA) through NAD-dependent activity.
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Background: The menstrual cycle in women is the main indicator of their reproductive health which is affected by the ongoing coronavirus disease 2019 (COVID-19) pandemic. This review aims to summarize the effects of the COVID-19 infection and the global pandemic on the menstrual health of women.

Methods: The literature search was conducted in PubMed, Cochrane library, and Google Scholar using keywords "COVID-19," "Menstrual Cycle," "Menstrual Cycle Irregularities," "Amenorrhea," "Polymenorrhea," and "Dysmenorrhea.

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Mitochondrial polymerase gamma (PolγA) is the only replicative polymerase in mitochondria. To determine PolγA ubiquitylation in cells, Flag-PolγA and MITOL are overexpressed, and subsequently the immunoprecipitated Flag-PolγA is checked for ubiquitylation. Alternately, in vitro synthesized PolγA and MITOL are used to determine whether PolγA is ubiquitylated.

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Monkeypox is a rare viral infection that is mostly concentrated in the regions of Central and West Africa. During the last couple of weeks, reports of confirmed monkeypox cases in non-endemic countries such as the United Kingdom have alerted health authorities in Pakistan as well. Keeping in mind the devastating effects of the recent COVID-19 pandemic on the healthcare system of Pakistan, a subsequent monkeypox outbreak can be catastrophic.

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This review article classifies chronic myeloid leukemia (CML) based on cytogenetic analyses and different mutations detected in CML patients. The use of advanced technologies, such as karyotyping, fluorescent in situ hybridization, and comparative genomic hybridization, has allowed us to study CML in detail and observe the different biochemical changes that occur in different CML types. This review also highlights the different types of receptor and signaling pathway mutations that occur in CML.

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Background Improving patient safety (PS) is critical to optimizing healthcare delivery. There is a need to develop curricula or incorporate PS concepts in health professionals' (HPs) education, in both theoretical and practical training. Consequently, there is a need to measure the perception of HPs regarding various PS competencies imparted to them during their training.

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Mutations in mitochondrial replicative polymerase PolγA lead to progressive external ophthalmoplegia (PEO). While PolγA is the known central player in mitochondrial DNA (mtDNA) replication, it is unknown whether a regulatory process exists on the mitochondrial outer membrane which controlled its entry into the mitochondria. We now demonstrate that PolγA is ubiquitylated by mitochondrial E3 ligase, MITOL (or MARCH5, RNF153).

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Defects in DNA repair pathways and alterations of mitochondrial energy metabolism have been reported in multiple skin disorders. More than 10% of patients with primary mitochondrial dysfunction exhibit dermatological features including rashes and hair and pigmentation abnormalities. Accumulation of oxidative DNA damage and dysfunctional mitochondria affect cellular homeostasis leading to increased apoptosis.

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Age and DNA repair deficiencies are strong risk factors for developing cancer. This is reflected in the comorbidity of cancer with premature aging diseases associated with DNA damage repair deficiencies. Recent research has suggested that DNA damage accumulation, telomere dysfunction and the accompanying mitochondrial dysfunction exacerbate the aging process and may increase the risk of cancer development.

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Background: An efficient inventory control system would help optimize the use of resources and eventually help improve patient care.

Objectives: The study aimed to find out the surgical consumables using always, better, and control (ABC) and vital, essential, and desirable (VED) technique as well as calculating the lead time of specific category A and vital surgical consumables.

Methods: This was a descriptive, record-based study conducted from January to March 2016 in the surgical stores of the All India Institute of Medical Sciences, New Delhi.

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Article Synopsis
  • The gene for the tumor suppressor p53 is commonly mutated in cancer, and its levels are regulated by E3 ligases, particularly FBW7α, which targets p53 for degradation in various cancer cell lines.
  • FBW7α promotes the degradation of both normal and mutated forms of p53 by attaching polyubiquitin chains to specific sites on p53 after it is phosphorylated, particularly after DNA damage events.
  • The absence of FBW7α leads to higher p53 levels and increased tumorigenic potential in cells, indicating a feedback loop where p53 can also activate FBW7, highlighting the complex regulation of p53 in response to DNA damage.
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The knowledge of the skeletal maturation and the stage of the growth of the patients seeking orthodontic treatment are of great value in planning efficient orthodontic therapy. However, different craniofacial structures of patient show variation in growth potential. The routine use of hand-wrist radiograph for growth prediction exposes the patient to extra radiation.

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Mutations in BLM helicase predispose Bloom syndrome (BS) patients to a wide spectrum of cancers. We demonstrate that MIB1-ubiquitylated BLM in G1 phase functions as an adaptor protein by enhancing the binding of transcription factor c-Jun and its E3 ligase, Fbw7α. BLM enhances the K48/K63-linked ubiquitylation on c-Jun, thereby enhancing the rate of its subsequent degradation.

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Germline mutations in RECQL4 helicase are associated with Rothmund-Thomson syndrome, which is characterized by a predisposition to cancer. RECQL4 localizes to the mitochondria, where it acts as an accessory factor during mitochondrial DNA replication. To understand the specific mitochondrial functions of RECQL4, we created isogenic cell lines, in which the mitochondrial localization of the helicase was either retained or abolished.

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Unlabelled: Germline mutations in RECQL4 and p53 lead to cancer predisposition syndromes, Rothmund-Thomson syndrome (RTS) and Li-Fraumeni syndrome (LFS), respectively. RECQL4 is essential for the transport of p53 to the mitochondria under unstressed conditions. Here, we show that both RECQL4 and p53 interact with mitochondrial polymerase (PolγA/B2) and regulate its binding to the mitochondrial DNA (mtDNA) control region (D-loop).

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