Browsing by Author "Reddy, Arubala P. (TTU)"
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Item A Combination Therapy of Urolithin A+EGCG Has Stronger Protective Effects than Single Drug Urolithin A in a Humanized Amyloid Beta Knockin Mice for Late-Onset Alzheimer’s Disease(2022) Kshirsagar, Sudhir; Alvir, Rainier Vladlen; Pradeepkiran, Jangampalli Adi; Hindle, Ashly; Vijayan, Murali; Ramasubramaniam, Bhagavathi; Kumar, Subodh; Reddy, Arubala P. (TTU); Reddy, P. Hemachandra (TTU)In the current study, for the first time, we study mitophagy enhancer urolithin A and a combination of urolithin A+green tea extract EGCG against human Aβ peptide-induced mitochondrial and synaptic, dendritic, inflammatory toxicities and behavioral changes in humanized homozygous amyloid beta knockin (hAbKI) mice of late-onset Alzheimer’s disease (AD). Our findings reveal significantly increased positive effects of urolithin A and a combination treatment of urolithin A+EGCG in hAbKI mice for phenotypic behavioral changes including motor coordination, locomotion/exploratory activity, spatial learning and working memory. mRNA and protein levels of mitochondrial fusion, synaptic, mitophagy and autophagy genes were upregulated, and mitochondrial fission genes are downregulated in urolithin A and combine treatment in hAbKI mice; however, the effect is stronger in combined treatment. Immunofluorescence analysis of hippocampal brain sections shows similar findings of mRNA and protein levels. Mitochondrial dysfunction is significantly reduced in both treatment groups, but a stronger reduction is observed in combined treatment. Dendritic spines and lengths are significantly increased in both treatment groups, but the effect is stronger in combined treatment. The fragmented number of mitochondria is reduced, and mitochondrial length is increased, and mitophagosomal formations are increased in both the groups, but the effect is stronger in the combined treatment. The levels of amyloid beta (Aβ) 40 and Aβ42 are reduced in both treatments, however, the reduction is higher for combined treatment. These observations suggest that urolithin A is protective against human Aβ peptide-induced toxicities; however, combined treatment of urolithin A+EGCG is effective and stronger, indicating that combined therapy is promising to treat late-onset AD patients.Item Current Status of Obesity: Protective Role of Catechins(2023) Basu, Tanisha (TTUHSC); Selman, Ashley (TTUHSC); Reddy, Arubala P. (TTU); Reddy, P. Hemachandra (TTUHSC)Obesity is a growing health concern in today’s society. Current estimates indicate that obesity occurs in both adults and young people. Recent research also found that the Hispanic population in the U.S. is 1.9 times more likely to be overweight as compared to their non-Hispanic population. Obesity is a multifactorial disease that has a variety of causes. All current treatment options incorporate dietary changes aimed at establishing a negative energy balance. According to current scientific research, multiple factors are involved with the development of obesity, including genetic, biochemical, psychological, environmental, behavioral, and socio-demographic factors. The people who suffer from obesity are far more likely to suffer serious health problems, such as stroke, diabetes, lung disease, bone and joint disease, cancer, heart disease, neurological disorders, and poor mental health. Studies indicate that multiple cellular changes are implicated in the progression of obesity, mitochondrial dysfunction, deregulated microRNAs, inflammatory changes, hormonal deregulation, and others. This article highlights the role that oxidative stress plays in obesity and current obesity-prevention techniques with an emphasis on the impact of catechins to prevent and treat obesity.Item Rlip Reduction Induces Oxidative Stress and Mitochondrial Dysfunction in Mutant Tau-Expressed Immortalized Hippocampal Neurons: Mechanistic Insights(2023) Reddy, P. Hemachandra (TTUHSC); Kshirsagar, Sudhir (TTUHSC); Bose, Chhanda (TTUHSC); Pradeepkiran, Jangampalli Adi (TTUHSC); Hindle, Ashly (TTUHSC); Singh, Sharda P. (TTUHSC); Reddy, Arubala P. (TTU); Baig, Javaria (TTUHSC)RalBP1 (Rlip) is a stress-activated protein that is believed to play a large role in aging and neurodegenerative diseases such as Alzheimer’s disease (AD) and other tauopathies. The purpose of our study was to understand the role of Rlip in mutant Tau-expressed immortalized hippocampal HT22 cells. In the current study, we used mutant Tau (mTau)-expressed HT22 neurons and HT22 cells transfected with Rlip-cDNA and/or silenced RNA, and studied the cell survival, mitochondrial respiration, mitochondrial function, immunoblotting, and immunofluorescence analysis of synaptic and mitophagy proteins and the colocalization of Rlip and mTau proteins. We found Rlip protein levels were reduced in mTau-HT22 cells, Rlip silenced HT22 cells, and mTau + Rlip RNA silenced HT22 cells; on the other hand, increased Rlip levels were observed in Rlip cDNA transfected HT22 cells. We found cell survival was decreased in mTau-HT22 cells and RNA-silenced HT22 cells. However, cell survival was increased in Rlip-overexpressed mTau-HT22 cells. A significantly reduced oxygen consumption rate (OCR) was found in mTau-HT22 cells and in RNA-silenced Rlip-HT22 cells, with an even greater reduction in mTau-HT22 + Rlip RNA-silenced HT22 cells. A significantly increased OCR was found in Rlip-overexpressed HT22 cells and in all groups of cells that overexpress Rlip cDNA. Mitochondrial function was defective in mTau-HT22 cells, RNA silenced Rlip in HT22 cells, and was further defective in mTau-HT22 + Rlip RNA-silenced HT22 cells; however, it was rescued in Rlip overexpressed in all groups of HT22 cells. Synaptic and mitophagy proteins were decreased in mTau-HT22 cells, and further reductions were found in RNA-silenced mTau-HT22 cells. However, these were increased in mTau + Rlip-overexpressed HT22 cells. An increased number of mitochondria and decreased mitochondrial length were found in mTau-HT22 cells. These were rescued in Rlip-overexpressed mTau-HT22 cells. These observations strongly suggest that Rlip deficiency causes oxidative stress/mitochondrial dysfunction and Rlip overexpression reverses these defects. Overall, our findings revealed that Rlip is a promising new target for aging, AD, and other tauopathies/neurological diseases.Item Support Provided by Caregivers for Community-Dwelling Obesity Individuals: Focus on Elderly and Hispanics(2023) Basu, Tanisha (TTUHSC); Sehar, Ujala (TTUHSC); Selman, Ashley (TTUHSC); Reddy, Arubala P. (TTU); Reddy, P. Hemachandra (TTUHSC)Obesity is a chronic disease marked by the buildup of extra adipose tissue and a higher chance of developing concomitant illnesses such as heart disease, diabetes, high blood pressure, and some malignancies. Over the past few decades, there has been a global increase in the prevalence of obesity, which now affects around one-third of the world’s population. According to recent studies, a variety of factors, including genetics and biology as well as environmental, physiological, and psychosocial factors, may have a role in the development of obesity. The prevalence of obesity is often higher among Hispanic American groups than among White people in the U.S. Obesity is a widespread condition with a high risk of morbidity and death, and it is well-recognized that the prevalence of comorbidities rises with rising levels of obesity or body mass index. To combat the rising prevalence of obesity in the USA, especially among Hispanics, one of the fastest-growing racial/ethnic groups in the country, there is an urgent need for obesity therapies. The exact cause of this disparity is unclear, but some responsible factors are a lack of education, high unemployment rates, high levels of food insecurity, an unhealthy diet, inadequate access to physical activity resources, a lack of health insurance, and constricted access to culturally adequate healthcare. Additionally, managing obesity and giving needed/timely support to obese people is a difficult responsibility for medical professionals and their loved ones. The need for caregivers is increasing with the increased number of individuals with obesity, particularly Hispanics. Our article summarizes the status of obesity, focusing on Hispanic populations, and we also highlight specific factors that contribute to obesity, including genetics, epigenetics, biological, physiological, and psychosocial factors, medication and disease, environment, and socio-demographics. This article also reviews caregiver duties and challenges associated with caring for people with obesity.