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81.
Abhimanyu Garg Wee-Teik Keng Zhenkang Chen Adwait Amod Sathe Chao Xing Pavithira Devi Kailasam Yanqiu Shao Nicholas P. Lesner Claire B. Llamas Anil K. Agarwal Prashant Mishra 《The Journal of clinical investigation》2022,132(23)
Multiple genetic loci have been reported for progeroid syndromes. However, the molecular defects in some extremely rare forms of progeria have yet to be elucidated. Here, we report a 21-year-old man of Chinese ancestry who has an autosomal recessive form of progeria, characterized by severe dwarfism, mandibular hypoplasia, hyperopia, and partial lipodystrophy. Analyses of exome sequencing data from the entire family revealed only 1 rare homozygous missense variant (c.86C>T; p.Pro29Leu) in TOMM7 in the proband, while the parents and 2 unaffected siblings were heterozygous for the variant. TOMM7, a nuclear gene, encodes a translocase in the outer mitochondrial membrane. The TOMM complex makes up the outer membrane pore, which is responsible for importing many preproteins into the mitochondria. A proteomic comparison of mitochondria from control and proband-derived cultured fibroblasts revealed an increase in abundance of several proteins involved in oxidative phosphorylation, as well as a reduction in abundance of proteins involved in phospholipid metabolism. We also observed elevated basal and maximal oxygen consumption rates in the fibroblasts from the proband as compared with control fibroblasts. We concluded that altered mitochondrial protein import due to biallelic loss-of-function TOMM7 can cause severe growth retardation and progeroid features. 相似文献
82.
Xun Wang Yuemeng Jia Jiawei Zhao Nicholas P. Lesner Cameron J. Menezes Spencer D. Shelton Siva Sai Krishna Venigalla Jian Xu Chunyu Cai Prashant Mishra 《The Journal of clinical investigation》2022,132(23)
A fundamental issue in regenerative medicine is whether there exist endogenous regulatory mechanisms that limit the speed and efficiency of the repair process. We report the existence of a maturation checkpoint during muscle regeneration that pauses myofibers at a neonatal stage. This checkpoint is regulated by the mitochondrial protein mitofusin 2 (Mfn2), the expression of which is activated in response to muscle injury. Mfn2 is required for growth and maturation of regenerating myofibers; in the absence of Mfn2, new myofibers arrested at a neonatal stage, characterized by centrally nucleated myofibers and loss of H3K27me3 repressive marks at the neonatal myosin heavy chain gene. A similar arrest at the neonatal stage was observed in infantile cases of human centronuclear myopathy. Mechanistically, Mfn2 upregulation suppressed expression of hypoxia-induced factor 1α (HIF1α), which is induced in the setting of muscle damage. Sustained HIF1α signaling blocked maturation of new myofibers at the neonatal-to-adult fate transition, revealing the existence of a checkpoint that delays muscle regeneration. Correspondingly, inhibition of HIF1α allowed myofibers to bypass the checkpoint, thereby accelerating the repair process. We conclude that skeletal muscle contains a regenerative checkpoint that regulates the speed of myofiber maturation in response to Mfn2 and HIF1α activity. 相似文献
83.
Gauri Mishra Anouk Dev Eldho Paul William Kemp Ammar Majeed John Lubel Sally Bell Paul Gow Amanda Nicoll Siddharth Sood Alex Thompson Marno Ryan Stuart K.Roberts 《肝癌研究(英文版)》2021,(7):66-79
Aim: Transarterial chemoembolisation (TACE) is recommended therapy for intermediate-stage hepatocellular carcinoma (HCC). However, the wide variations in outcom... 相似文献
84.
John Monro Suman Mishra Halina Stoklosinski Kerry Bentley-Hewitt Duncan Hedderley Hannah Dinnan Sheridan Martell 《Nutrients》2022,14(15)
Non-sugar components of kiwifruit reduce the amplitude of the glycaemic response to co-consumed cereal starch. We determined the relative contribution of different non-sugar kiwifruit components to this anti-glycaemic effect. Healthy participants (n = 9) ingested equal carbohydrate meals containing 20 g starch as wheat biscuit (WB, 30 g), and the sugar equivalent of two kiwifruit (KFsug, 20.4 g), either intrinsic or added as glucose, fructose and sucrose (2:2:1). The meals were WB+KFsug (control, no non-sugar kiwifruit components), WB + whole kiwifruit pulp (WB+KF), WB + neutralised kiwifruit pulp (WB+KFneut), WB + low-fibre kiwifruit juice (WB+KFjuice) and WB+KFsug + kiwifruit organic acids (WB+KFsug+OA). All meals were spiked with 100 mg sodium [1-13C] acetate to measure intestinal absorption. Each participant ingested all meals in random order. Blood glucose and breath 13CO2 were measured at ingestion and at 15 min intervals up to 180 min. Compared with WB+KFsug, whole kiwifruit pulp (WB+KF) almost halved glycaemic response amplitude (p < 0.001), reduced incremental area under the blood glucose response curve (iAUC) at 30 min (peak) by 50% (p < 0.001), and averted late postprandial hypoglycaemia. All other treatments suppressed response amplitude half as much as whole kiwifruit and averted acute hypoglycaemia, with little effect on iAUC. Effects on 13CO2 exhalation paralleled effects on blood glucose (R2 = 0.97). Dietary fibre and organic acids contributed equally to the anti-glycaemic effect of kiwifruit by reducing intestinal absorption rate. Kiwifruit flesh effectively attenuates glycaemic response in carbohydrate exchange, as it contains fructose, dietary fibre and organic acids. 相似文献
85.
Working Group on Pediatric Acute Rheumatic Fever Cardiology Chapter of Indian Academy of Pediatrics Saxena A Kumar RK Gera RP Radhakrishnan S Mishra S Ahmed Z 《Indian pediatrics》2008,45(7):565-573
JUSTIFICATION: Acute rheumatic fever and rheumatic chronic valvular heart disease is an important preventable cause of morbidity and mortality in suburban and rural India. Its diagnosis is based on clinical criteria. These criteria need verification and revision in the Indian context. Furthermore, there are glaring differences in management protocols available in literature. These facts prompted Indian Academy of Pediatrics to review the management of rheumatic fever. PROCESS: Management of Rheumatic fever was reviewed and recommendation was formulated at national consultative meeting on 20th May 2007 at New Delhi. OBJECTIVES: To formulate uniform guidelines on management of acute rheumatic fever and rheumatic heart disease in the Indian context. Guidelines were formulated for the management of streptococcal pharyngitis, acute rheumatic fever and its cardiac complication as well as secondary prophylaxis for recurrent episodes. RECOMMENDATIONS: (1) Streptococcal eradication with appropriate antibiotics (Benzathine penicillin single dose or penicillin V oral or azithromycin). (2) Diagnosis of rheumatic fever based on Jones criteria. (3) Control inflammatory process with aspirin with or without steroids (total duration of treatment of 12 weeks). (4) Treatment of chorea according to severity (therapy to continue for 2-3 weeks after clinical improvement). (5) Protocol for managing cardiac complication like valvular heart disease, congestive heart failure and atrial fibrillation. (6) Secondary prophylaxis with benzathine penicillin and management of anaphylaxis. 相似文献
86.
Panchanan Sahoo Sudip Kundu Shubham Roy S. K. Sharma Jiten Ghosh Snehasis Mishra Abhishek Mukherjee Chandan Kumar Ghosh 《RSC advances》2022,12(38):24555
A targeted multimodal strategy on a single nanoplatform is attractive in the field of nanotheranostics for the complete ablation of cancer. Herein, we have designed mesoporous silica (m-SiO2)-coated Prussian blue nanocubes (PBNCs), functionalized with hyaluronic acid (HA) to construct a multifunctional PBNC@m-SiO2@HA nanoplatform that exhibited good biocompatibility, excellent photodynamic activity, and in vitro T1-weighted magnetic resonance imaging ability (r1 ∼ 3.91 mM−1 s−1). After loading doxorubicin into the as-prepared PBNC@m-SiO2@HA, the developed PBNC@m-SiO2@HA@DOX displayed excellent pH-responsive drug release characteristics. Upon irradiation with 808 nm (1.0 W cm−2) laser light, PBNC@m-SiO2@HA@DOX exhibited synergistic photodynamic and chemotherapeutic efficacy (∼78% in 20 minutes) for human colorectal carcinoma (HCT 116) cell line compared to solo photodynamic or chemotherapy. Herein, the chemo-photodynamic therapeutic process was found to follow the apoptotic pathway via ROS-mediated mitochondrion-dependent DNA damage with a very low cellular uptake of PBNC@m-SiO2@HA@DOX for the human embryonic kidney (HEK 293) cell line, illustrating its safety. Hence, it may be stated that the developed nanoplatform can be a potential theranostic agent for future applications. Most interestingly, we have noted variation in r1 at each step of the functionalization along with size variation that has been the first time modelled on the basis of the Solomon–Bloembergen–Morgan theory considering changes in the defect crystal structure, correlation time, water diffusion rate, etc., due to varied interactions between PBNC and water molecules.A targeted multimodal strategy on a single nanoplatform is attractive in the field of nanotheranostics for the complete ablation of cancer. 相似文献
87.
Kamal Kant Sahu Ajay Kumar Mishra Amos Lal Ahmad Daniyal Siddiqui Susan VGeorge 《世界急诊医学杂志(英文)》2021,12(1):81
Dear editor,We congratulate Chowdhury et al[1] for their excellentreport and successful management of a young ladysuffering from cocaine-induced methemoglobinemia.Through this letter, we aim to address some additionalconcerns, which would certainly be helpful for acomplete understanding of this topic. 相似文献
88.
89.
Mamta Singh Deepak Mishra Bibhuti P Sinha Abhishek Anand Shubha Singhal 《Indian journal of ophthalmology》2022,70(11):3791
Cataract causes bilateral blindness in 20 million people globally, the vast majority of whom live in developing countries. Manual small-incision cataract surgery (MSICS) has emerged as an efficient and economical alternative to phacoemulsification, giving comparable results in terms of final visual gain. One of the important determinants of postoperative visual gain is the status of the corneal endothelium. Multiple factors such as corneal distortion, irrigation solution turbulence, mechanical trauma by instruments, nuclear fragments, intraocular lens contact, and free oxygen radicals, all have been implicated in causing corneal damage during cataract surgery. MSICS with posterior chamber intraocular lens implantation has been reported to cause an endothelial cell loss of 15.83%, which is comparable with other modes of cataract surgery like extracapsular cataract extraction and phacoemulsification. Thorough preoperative assessment of endothelial status and taking necessary steps for endothelial protection during surgery can decrease the endothelial cell loss and overall burden of pseudophakic bullous keratopathy. In addition to surgical techniques, the type of irrigating solutions, ocular viscoelastic devices, intracameral dyes, and drugs all affect the endothelial cell status. This review presents a summary of available literature on the protection of endothelial cells during different steps of MSICS. This is especially relevant for developing countries where large-scale MSICS cataract surgeries are performed to decrease the cataract blindness burden. 相似文献
90.
Aradhna Mishra Mohammad Ashraf Simi Zaka-ur-Rab Nida Khan 《Indian journal of ophthalmology》2022,70(12):4337
Purpose:To determine the retinal nerve fiber layer (RNFL) thickness and ganglion cell complex (GCC) thickness in patients having relative afferent pupillary defect (RAPD) measured by optical coherence tomography (OCT).Methods:This cross-sectional study was conducted on 30 patients with posterior segment disease and glaucoma presenting with RAPD. The control group comprised 30 patients with the aforementioned diseases without RAPD. RAPD was graded using neutral density filters placed over the unaffected eye. Peripapillary RNFL thickness and macular GCC were measured using the Cirrus HD-OCT machine.Results:There were 45 males and 15 females. There was a statistically significant (P < 0.05) difference in the mean of average RNFL thickness in patients having RAPD (64.73 ± 15.16 mm in the affected eyes) as compared to sick control (82.73 ± 11.33 mm in the affected eyes). It was further observed that there was a decrease in RNFL thickness with advancing grades of RAPD. There was a statistically significant (P < 0.05) difference in the mean of average GCC thickness in patients having RAPD (51.57 ± 14.96 mm in the affected eyes) as compared to sick control (76.36 ± 8.06 mm in the affected eyes).Conclusion:Our study suggests that there is a significant reduction in RNFL thickness and GCC thickness in RAPD patients as compared to the sick control group. 相似文献