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Article ; Online: Targeting neuromuscular junction to treat neuromuscular disorders.

Qaisar, Rizwan

2023 Volume 333, Page(s) 122186

Abstract: The integrity and preservation of the neuromuscular junction (NMJ), the interface between the motor neuron and skeletal muscle, is critical for maintaining a healthy skeletal muscle. The structural and/or functional defects in the three cellular ... ...

Abstract	The integrity and preservation of the neuromuscular junction (NMJ), the interface between the motor neuron and skeletal muscle, is critical for maintaining a healthy skeletal muscle. The structural and/or functional defects in the three cellular components of NMJ, namely the pre-synaptic terminal, synaptic cleft, and post-synaptic region, negatively affect skeletal muscle mass and/or strength. Therefore, NMJ repair appears to be an appropriate therapy for muscle disorders. Mouse models provide a detailed molecular characterization of various cellular components of NMJ with relevance to human diseases. This review discusses different molecular targets on the three cellular components of NMJ for treating muscle diseases. The potential effects of these therapies on NMJ morphology and motor performance, their therapeutic efficacy, and clinical relevance are discussed. Collectively, the available data supports targeting NMJ alone or as an adjunct therapy in treating muscle disorders. However, the potential impact of such interventions on human patients with muscle disorders requires further investigation.
MeSH term(s)	Mice ; Animals ; Humans ; Neuromuscular Junction/physiology ; Neuromuscular Diseases/drug therapy ; Synapses/physiology ; Muscle, Skeletal ; Muscular Diseases
Language	English
Publishing date	2023-10-17
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	3378-9
ISSN	1879-0631 ; 0024-3205
ISSN (online)	1879-0631
ISSN	0024-3205
DOI	10.1016/j.lfs.2023.122186
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Article ; Online: Nanomedicine for Treating Muscle Dystrophies: Opportunities, Challenges, and Future Perspectives.

Ahmed, Zaheer / Qaisar, Rizwan

International journal of molecular sciences

2022 Volume 23, Issue 19

Abstract: Muscular dystrophies are a group of genetic muscular diseases characterized by impaired muscle regeneration, which leads to pathological inflammation that drives muscle wasting and eventually results in weakness, functional dependency, and premature ... ...

Abstract	Muscular dystrophies are a group of genetic muscular diseases characterized by impaired muscle regeneration, which leads to pathological inflammation that drives muscle wasting and eventually results in weakness, functional dependency, and premature death. The most known causes of death include respiratory muscle failure due to diaphragm muscle decay. There is no definitive treatment for muscular dystrophies, and conventional therapies aim to ameliorate muscle wasting by promoting physiological muscle regeneration and growth. However, their effects on muscle function remain limited, illustrating the requirement for major advancements in novel approaches to treatments, such as nanomedicine. Nanomedicine is a rapidly evolving field that seeks to optimize drug delivery to target tissues by merging pharmaceutical and biomedical sciences. However, the therapeutic potential of nanomedicine in muscular dystrophies is poorly understood. This review highlights recent work in the application of nanomedicine in treating muscular dystrophies. First, we discuss the history and applications of nanomedicine from a broader perspective. Second, we address the use of nanoparticles for drug delivery, gene regulation, and editing to target Duchenne muscular dystrophy and myotonic dystrophy. Next, we highlight the potential hindrances and limitations of using nanomedicine in the context of cell culture and animal models. Finally, the future perspectives for using nanomedicine in clinics are summarized with relevance to muscular dystrophies.
MeSH term(s)	Animals ; Muscle, Skeletal/pathology ; Muscles/pathology ; Muscular Atrophy/pathology ; Muscular Dystrophy, Duchenne/drug therapy ; Muscular Dystrophy, Duchenne/genetics ; Myotonic Dystrophy/pathology ; Nanomedicine ; Pharmaceutical Preparations
Chemical Substances	Pharmaceutical Preparations
Language	English
Publishing date	2022-10-10
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms231912039
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Article: Editorial: Skeletal muscle in age-related diseases: From molecular pathogenesis to potential interventions.

Parvatiyar, Michelle S / Qaisar, Rizwan

Frontiers in physiology

2022 Volume 13, Page(s) 1056479

Language	English
Publishing date	2022-10-17
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2022.1056479
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Article ; Online: A comparison of international and national references to measure the prevalence of stunting in Pakistani school-age girls.

Qaisar, Rizwan / Karim, Asima

Scientific reports

2022 Volume 12, Issue 1, Page(s) 5501

Abstract: Epidemiology of stunting in < 5 years old is well characterized; however, its prevalence in adolescence is inconsistent in different geographical locations. We estimated the prevalence of stunting in schoolgirls of Punjab, Pakistan, to standardize local ... ...

Abstract	Epidemiology of stunting in < 5 years old is well characterized; however, its prevalence in adolescence is inconsistent in different geographical locations. We estimated the prevalence of stunting in schoolgirls of Punjab, Pakistan, to standardize local references according to international and national references. In this population-wide cross-sectional study, 10,050 schoolgirls aged 8-16 years from 12 different districts of northern, central, and southern Punjab were analyzed. The prevalence of stunting was calculated by applying Centres for Disease Control and Prevention (CDC) and World Health Organisation (WHO) height-for-age references and the local reference for the study population. We used Cohen's kappa statistics to analyze the agreement of our data with reference values, and chi-square test was used as the test of trend. Marked overestimation of the prevalence of stunting was observed (22.72% and 17.49% according to CDC and WHO, respectively) in comparison to local reference (4.94%). According to CDC and WHO references, there was an increasing trend of prevalence of stunting with higher age; however, data was comparable across all the age groups when local references were applied. We recommend that the prevalence of stunting in school-age girls should be determined by applying local height references rather than international ones to plan health strategies and treatments in the local population.
MeSH term(s)	Adolescent ; Body Height ; Child ; Child, Preschool ; Cross-Sectional Studies ; Female ; Growth Disorders/epidemiology ; Humans ; Pakistan/epidemiology ; Prevalence
Language	English
Publishing date	2022-04-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-09511-3
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Article ; Online: Butyrate supplementation reduces sarcopenia by repairing neuromuscular junction in patients with chronic obstructive pulmonary disease.

Qaisar, Rizwan / Karim, Asima / Muhammad, Tahir / Ahmad, Firdos

Respiratory medicine

2023 Volume 222, Page(s) 107510

Abstract: Introduction: Chronic obstructive pulmonary disease (COPD) is associated with an intestinal leak and neuromuscular junction (NMJ) degradation, which contributes to physical compromise and accelerated age-related muscle loss, called sarcopenia. However, ... ...

Abstract	Introduction: Chronic obstructive pulmonary disease (COPD) is associated with an intestinal leak and neuromuscular junction (NMJ) degradation, which contributes to physical compromise and accelerated age-related muscle loss, called sarcopenia. However, the relevant interventions partly remain ineffective. We investigated the effects of exogenous butyrate on sarcopenia and physical capacity with relevance to intestinal permeability and NMJ integrity in COPD patients. Methods: COPD patients were randomized into placebo (n = 67) and butyrate (n = 64) groups in a double-blind manner. The patients in the butyrate group received one 300 mg capsule a day for 12 weeks. We measured circulating markers of intestinal leak (zonulin), systemic bacterial load (LBP), and NMJ loss (CAF22), along with handgrip strength (HGS), and short physical performance battery (SPPB) at baseline and 12 weeks. Results: Butyrate supplementation improved HGS and gait speed in COPD patients. Among SPPB indices, butyrate improved the ability to maintain postural balance and walking and prevented a decline in the ability to rise from a chair. Butyrate also reduced the plasma levels of zonulin, LBP, and CAF22 levels in COPD patients (all p < 0.05). Regression analysis revealed significant associations of plasma zonulin and CAF22 with HGS, gait speed, and cumulative SPPB scores in butyrate group. These changes were associated with reduced markers of inflammation and muscle damage. Conclusion: Butyrate may provide a therapeutic approach to sarcopenia and physical dependency in COPD by repairing intestinal leak and NMJ loss.
MeSH term(s)	Humans ; Sarcopenia/etiology ; Sarcopenia/prevention & control ; Hand Strength/physiology ; Butyrates ; Pulmonary Disease, Chronic Obstructive/complications ; Pulmonary Disease, Chronic Obstructive/drug therapy ; Neuromuscular Junction ; Dietary Supplements
Chemical Substances	Butyrates
Language	English
Publishing date	2023-12-22
Publishing country	England
Document type	Randomized Controlled Trial ; Journal Article
ZDB-ID	1003348-8
ISSN	1532-3064 ; 0954-6111
ISSN (online)	1532-3064
ISSN	0954-6111
DOI	10.1016/j.rmed.2023.107510
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Article ; Online: Circulating H-FABP as a biomarker of frailty in patients with chronic heart failure.

Ahmad, Firdos / Karim, Asima / Khan, Javaidullah / Qaisar, Rizwan

Experimental biology and medicine (Maywood, N.J.)

2023 Volume 248, Issue 16, Page(s) 1383–1392

Abstract: Increased vulnerability to physiologic stressors, termed frailty, is a common occurrence in patients with chronic heart failure (CHF). However, the definite biomarkers to assess frailty in CHF patients are not known. Here, we assessed the frailty ... ...

Abstract	Increased vulnerability to physiologic stressors, termed frailty, is a common occurrence in patients with chronic heart failure (CHF). However, the definite biomarkers to assess frailty in CHF patients are not known. Here, we assessed the frailty phenotype and its potential association with heart failure (HF) markers in CHF patients. We categorized controls (
MeSH term(s)	Humans ; Biomarkers ; Chronic Disease ; Fatty Acid Binding Protein 3 ; Fatty Acid-Binding Proteins ; Frailty ; Galectin 3 ; Heart Failure ; Interleukin-1 Receptor-Like 1 Protein
Chemical Substances	Biomarkers ; Fatty Acid Binding Protein 3 ; Fatty Acid-Binding Proteins ; Galectin 3 ; Interleukin-1 Receptor-Like 1 Protein ; FABP1 protein, human
Language	English
Publishing date	2023-10-03
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	4015-0
ISSN	1535-3699 ; 1525-1373 ; 0037-9727
ISSN (online)	1535-3699 ; 1525-1373
ISSN	0037-9727
DOI	10.1177/15353702231198080
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Article ; Online: Plasma Galectin-3 and H-FABP correlate with poor physical performance in patients with congestive heart failure.

Ahmad, Firdos / Karim, Asima / Khan, Javaidullah / Qaisar, Rizwan

Experimental biology and medicine (Maywood, N.J.)

2023 Volume 248, Issue 6, Page(s) 532–540

Abstract: Heart failure (HF) is often associated with compromised physical capacity in patients. However, it is unclear if established HF markers correlate with the physical performance of patients with congestive HF (CHF). We assessed the left ventricular end- ... ...

Abstract	Heart failure (HF) is often associated with compromised physical capacity in patients. However, it is unclear if established HF markers correlate with the physical performance of patients with congestive HF (CHF). We assessed the left ventricular end-systolic dimension (LVESD) and ejection fraction (LVEF) and, physical performance parameters, including short physical performance battery (SPPB), gait speed (GS), and handgrip strength (HGS) in 80 patients with CHF along with 59 healthy controls. Furthermore, levels of plasma HF markers galectin-3 and heart-specific fatty acid binding protein (H-FABP) were measured in relation to the severity of HF and physical performance. Irrespective of etiology, significantly greater LVESD and lower LVEF were observed in HF patients versus controls. As expected, the levels of HF markers galectin-3 and H-FABP were upregulated in the CHF patients which were accompanied by significantly elevated levels of plasma zonulin and inflammatory marker C-reactive protein (CRP). The SPPB scores, GS, and HGS were significantly lower in the ischemic and non-ischemic HF patients than controls. The level of galectin-3 was inversely correlated with SPPB scores (
MeSH term(s)	Humans ; Biomarkers ; Fatty Acid Binding Protein 3 ; Galectin 3 ; Hand Strength ; Heart Failure
Chemical Substances	Biomarkers ; Fatty Acid Binding Protein 3 ; Galectin 3 ; LGALS3 protein, human ; FABP3 protein, human
Language	English
Publishing date	2023-02-19
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	4015-0
ISSN	1535-3699 ; 1525-1373 ; 0037-9727
ISSN (online)	1535-3699 ; 1525-1373
ISSN	0037-9727
DOI	10.1177/15353702231151980
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Article ; Online: Statin Therapy Induces Gut Leakage and Neuromuscular Disjunction in Patients With Chronic Heart Failure.

Ahmad, Firdos / Karim, Asima / Khan, Javaidullah / Qaisar, Rizwan

Journal of cardiovascular pharmacology

2023 Volume 82, Issue 3, Page(s) 189–195

Abstract: Abstract: Statins are commonly used to limit the risk of cardiovascular diseases, including ischemic heart attack and stroke. However, treatment often leads to myopathy and muscle weakness. Therefore, a better understanding of underlying pathomechanism ... ...

Abstract	Abstract: Statins are commonly used to limit the risk of cardiovascular diseases, including ischemic heart attack and stroke. However, treatment often leads to myopathy and muscle weakness. Therefore, a better understanding of underlying pathomechanism is needed to improve the clinical outcomes. Here, we assessed the physical performance, including handgrip strength (HGS), gait speed (GS), and short physical performance battery, in 172 patients diagnosed with chronic heart failure (CHF) treated with (n = 50) or without (n = 122) statin and 59 controls. The plasma biomarkers, including sarcopenia marker C-terminal agrin fragment-22 (CAF22), intestinal barrier integrity marker zonulin, and C-reactive protein (CRP), were measured and correlated with the physical performance of patients. The HGS, short physical performance battery scores, and GS were significantly compromised in patients with CHF versus controls. Irrespective of etiology, significant elevation of plasma CAF22, zonulin, and CRP was observed in patients with CHF. There were strong inverse correlations of CAF22 with HGS (r 2 = 0.34, P < 0.0001), short physical performance battery scores (r 2 = 0.08, P = 0.0001), and GS (r 2 = 0.143, P < 0.0001). Strikingly, CAF22 and zonulin were positively correlated with each other (r 2 = 0.10, P = 0.0002) and with the level of CRP in patients with CHF. Further investigations revealed a significant induction of CAF22, zonulin, and CRP in patients with CHF taking statin versus nonstatin group. Consistently, HGS and GS were significantly lower in the statin versus nonstatin CHF patients' group. Collectively, statin therapy adversely affects the neuromuscular junction and intestinal barrier, which potentially induces systemic inflammation and physical disability in patients with CHF. Further prospective confirmation of the findings is required in a well-controlled study.
MeSH term(s)	Humans ; Biomarkers/blood ; C-Reactive Protein/metabolism ; Case-Control Studies ; Chronic Disease ; Hand Strength/physiology ; Heart Failure/blood ; Heart Failure/diagnosis ; Heart Failure/drug therapy ; Heart Failure/physiopathology ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects ; Intestinal Mucosa/drug effects ; Intestinal Mucosa/physiopathology ; Neuromuscular Junction/drug effects ; Neuromuscular Junction/physiopathology ; Physical Functional Performance ; Walking Speed/physiology ; Male ; Middle Aged ; Aged
Chemical Substances	Biomarkers ; C-Reactive Protein (9007-41-4) ; C-terminal agrin fragment ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; zonulin
Language	English
Publishing date	2023-09-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	391970-5
ISSN	1533-4023 ; 0160-2446
ISSN (online)	1533-4023
ISSN	0160-2446
DOI	10.1097/FJC.0000000000001445
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Article ; Online: BMI status relative to international and national growth references among Pakistani school-age girls.

Qaisar, Rizwan / Karim, Asima

BMC pediatrics

2021 Volume 21, Issue 1, Page(s) 535

Abstract: Background: A sizable proportion of school-going children from developing countries has abnormal growth parameters, often not standardized with international reference values. We aimed to assess the prevalence of underweight, overweight, and obesity in ... ...

Abstract	Background: A sizable proportion of school-going children from developing countries has abnormal growth parameters, often not standardized with international reference values. We aimed to assess the prevalence of underweight, overweight, and obesity in the schoolgirls of Punjab according to international and local references. Methods: In this population-based cross-sectional study, 10,050 school-going girls aged 8-16 years from 12 districts of northern, central, and southern Punjab were recruited. Estimates of normal weight, underweight, overweight and obesity were calculated in the girls according to three international BMI references including centers for disease control (CDC) 2000, the international obesity task force (IOTF) 2012 and world health organisation (WHO) 2007 in addition to a local reference for the population under study. We used Cohen's kappa statistics to analyse the agreement of our data with reference values. Results: There was marked overestimation of underweight (23.9%, 14.5%, 15.2% and 4.37%), slight underestimation of overweight (5.3%, 7.3%, 7.9% and 8.97%) and moderate underestimation of obesity (1.9%, 1.5%, 2.2% and 5.67%) according to CDC, IOTF, WHO and local reference, respectively. When the weight status of the study cohort was compared with the local data, we found comparable results in all four weight categories. Conclusion: We recommend population-wide further studies to estimate the prevalence of weight status in school-age girls for devising appropriate references and for planning strategies for public health policy and management.
MeSH term(s)	Body Mass Index ; Body Weight ; Cross-Sectional Studies ; Female ; Humans ; Overweight/epidemiology ; Pakistan/epidemiology ; Prevalence ; Schools ; Thinness/epidemiology
Language	English
Publishing date	2021-12-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2041342-7
ISSN	1471-2431 ; 1471-2431
ISSN (online)	1471-2431
ISSN	1471-2431
DOI	10.1186/s12887-021-03017-z
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Article ; Online: Towards Understanding the Development of Breast Cancer: The Role of RhoJ in the Obesity Microenvironment.

Bou Malhab, Lara J / Nair, Vidhya A / Qaisar, Rizwan / Pintus, Gianfranco / Abdel-Rahman, Wael M

Cells

2024 Volume 13, Issue 2

Abstract: Obesity is a growing pandemic with an increasing risk of inducing different cancer types, including breast cancer. Adipose tissue is proposed to be a major player in the initiation and progression of breast cancer in obese people. However, the ... ...

Abstract	Obesity is a growing pandemic with an increasing risk of inducing different cancer types, including breast cancer. Adipose tissue is proposed to be a major player in the initiation and progression of breast cancer in obese people. However, the mechanistic link between adipogenicity and tumorigenicity in breast tissues is poorly understood. We used in vitro and in vivo approaches to investigate the mechanistic relationship between obesity and the onset and progression of breast cancer. In obesity, adipose tissue expansion and remodeling are associated with increased inflammatory mediator's release and anti-inflammatory mediators' reduction.. In order to mimic the obesity micro-environment, we cultured cells in an enriched pro-inflammatory cytokine medium to which we added a low concentration of beneficial adipokines. Epithelial cells exposed to the obesity micro-environment were phenotypically transformed into mesenchymal-like cells, characterized by an increase in different mesenchymal markers and the acquisition of the major hallmarks of cancerous cells; these include sustained DNA damage, the activation of the ATR-Chk2 pathway, an increase in proliferation rate, cell invasion, and resistance to conventional chemotherapy. Transcriptomic analysis revealed that several genes, including RhoJ, CCL7, and MMP9, acted as potential major players in the observed phenomenon. The transcriptomics findings were confirmed in vitro using qRT-PCR and in vivo using high-fat-diet-fed mice. Our data suggests RhoJ as a potential novel molecular driver of tumor development in breast tissues and a mediator of cell resistance to conventional chemotherapy through PAK1 activation. These data propose that RhoJ is a potential target for therapeutic interventions in obese breast cancer patients.
MeSH term(s)	Animals ; Female ; Humans ; Mice ; Adipokines ; Adiposity ; Breast Neoplasms/etiology ; Breast Neoplasms/genetics ; Obesity/complications ; Tumor Microenvironment ; rho GTP-Binding Proteins/genetics ; rho GTP-Binding Proteins/metabolism
Chemical Substances	Adipokines ; RHOJ protein, human (EC 3.6.1.-) ; Rhoj protein, mouse ; rho GTP-Binding Proteins (EC 3.6.5.2)
Language	English
Publishing date	2024-01-17
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells13020174
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