Simulated Chronic Jet Lag Affects the Structural and Functional Complexity of Hippocampal Neurons in Mice.

There has been a long history that chronic circadian disruption such as jet lag or shift work negatively affects brain and body physiology. Studies have shown that circadian misalignment act as a risk factor for developing anxiety and mood-related depression-like behavior. Till date, most studies focused on simulating jet lag in model animals under laboratory conditions by repeated phase advances or phase delay only, while the real-life conditions may differ. In the present study, adult male mice were subjected to simulated chronic jet lag (CJL) by alternately advancing and delaying the ambient light-dark (LD) cycle by 9 h every 2 days, thereby covering a total of 24 days. The effect of CJL was then examined for a range of stress and depression-related behavioral and physiological responses. The results showed that mice exposed to CJL exhibited depression-like behavior, such as anhedonia. In the open field and elevated plus maze test, CJL-exposed mice showed increased anxiety behavior compared to LD control. In addition, CJL-exposed mice showed an increased level of serum corticosterone and proinflammatory cytokine, TNF-α in both serum and hippocampus. Moreover, CJL-exposed mice exhibited a reduction in structural complexity of hippocampal CA1 neurons along with decreased expression of neurotrophic growth factors, BDNF and NGF in the hippocampus compared to LD control. Taken together, our findings suggest that simulated chronic jet lag adversely affects structural and functional complexity in hippocampal neurons along with interrelated endocrine and inflammatory responses, ultimately leading to stress, anxiety, and depression-like behavior in mice.

Saussurea costus (Falc.) Lipsch.: a comprehensive review of its pharmacology, phytochemicals, ethnobotanical uses, and therapeutic potential.

Saussurea costus (Falc.) Lipsch., commonly known as costus, is a perennial herb that has been traditionally used in various indigenous medicinal systems across Asia. Its historical prominence in traditional remedies underscores the need to explore its phytochemical composition, pharmacological properties, and potential therapeutic benefits. This review aims to provide a comprehensive overview of the available literature on the pharmacological properties, phytochemical constituents, ethnobotanical uses, and therapeutic potential of S. costus. An exhaustive search was performed across multiple electronic databases, including PubMed/MedLine, Google Scholar, Web of Science, Scopus, TRIP database, and Science Direct. Both experimental and clinical studies, as well as traditional ethnobotanical records, were considered for inclusion. The phytochemical analysis revealed that S. costus contains a plethora of bioactive compounds, including sesquiterpenes, flavonoids, and essential oils, which are responsible for its myriad of medicinal properties. The pharmacological studies have demonstrated its anti-inflammatory, anti-oxidant, anti-cancer, hepatoprotective, and immunomodulatory effects, among others. Ethnobotanical data showcased its extensive use in treating ailments like asthma, digestive disorders, and skin conditions. Some clinical trials also underscore its efficacy in certain health conditions, corroborating its traditional uses. S. costus possesses significant therapeutic potential, largely attributable to its rich phytochemical composition; the convergence of its traditional uses and modern pharmacological findings suggests promising avenues for future research, especially in drug development and understanding its mechanism of action in various ailments.

Mechanistic role and potential of Ayurvedic herbs as anti-aging therapies.

INTRODUCTION: Medicinal plants and herbs are the most important part of the Ayurveda. The term Rasayana in Charaka Samhita confers long life, youthfulness, strong body, freedom from diseases and the plants mentioned in Rsayana possess antiaging property. Aging is the collective term used for the complex detrimental physiological changes that reduce the functional ability of the cell. Oxidative stress, telomeres shortening, inflammation, and mitochondrial dysfunction are the main factors that regulate the aging process. Chronological aging is an irreversible process but the factors causing biological aging can be controlled. Ayurvedic herbs are better for the management of age-related problems. There are several natural bioactive agents present in plants that can delay the aging process in humans. They trigger actions like enhancing gene longevity and telomerase activity, ROS scavenging furthermore regeneration of tissues. CONTENT: The plants mentioned in the Rasayana of Ayurveda have antiaging potential and can be used to solve modern problems related to aging. Some Ayurvedic plants and their antiaging potential has explained in this review. The main causes of aging, medicinal plants and their use as potential antiaging mediator are covered in this study. SUMMARY: The process of aging is still an enigma. It is a complex, irretrievable, dynamic process that involves a number of factors and is subject to a number of environmental and genetic influences. Rasayana aspect has not been much investigated in clinical trials. Aging is considered to result from free radical damage. According to Charaka, Rasayana drugs open the partially or fully blocked channels. Many Rasayanas show free radical scavenging activity and has the potential to mitigate the effects of aging. It gives an overview of the significance of Ayurvedic medicinal plants as a source of inspiration and the use of these plants as remedies for antiaging. OUTLOOK: This study briefly outlooks the causes of aging and how medicinal plants can be used to reverse the aging process. In this study, we discussed the antiaging potential and mechanistic roles of Ayurvedic herbs. These herbs have the properties to slow down the natural process of aging and can successfully manage common age-related problems.

Mechanistic role and potential of Ayurvedic herbs as anti-aging therapies.

INTRODUCTION: Medicinal plants and herbs are the most important part of the Ayurveda. The term Rasayana in Charaka Samhita confers long life, youthfulness, strong body, freedom from diseases and the plants mentioned in Rsayana possess antiaging property. Aging is the collective term used for the complex detrimental physiological changes that reduce the functional ability of the cell. Oxidative stress, telomeres shortening, inflammation, and mitochondrial dysfunction are the main factors that regulate the aging process. Chronological aging is an irreversible process but the factors causing biological aging can be controlled. Ayurvedic herbs are better for the management of age-related problems. There are several natural bioactive agents present in plants that can delay the aging process in humans. They trigger actions like enhancing gene longevity and telomerase activity, ROS scavenging furthermore regeneration of tissues. CONTENT: The plants mentioned in the Rasayana of Ayurveda have antiaging potential and can be used to solve modern problems related to aging. Some Ayurvedic plants and their antiaging potential has explained in this review. The main causes of aging, medicinal plants and their use as potential antiaging mediator are covered in this study. SUMMARY: The process of aging is still an enigma. It is a complex, irretrievable, dynamic process that involves a number of factors and is subject to a number of environmental and genetic influences. Rasayana aspect has not been much investigated in clinical trials. Aging is considered to result from free radical damage. According to Charaka, Rasayana drugs open the partially or fully blocked channels. Many Rasayanas show free radical scavenging activity and has the potential to mitigate the effects of aging. It gives an overview of the significance of Ayurvedic medicinal plants as a source of inspiration and the use of these plants as remedies for antiaging. OUTLOOK: This study briefly outlooks the causes of aging and how medicinal plants can be used to reverse the aging process. In this study, we discussed the antiaging potential and mechanistic roles of Ayurvedic herbs. These herbs have the properties to slow down the natural process of aging and can successfully manage common age-related problems.

Autophagy promotes cell survival by maintaining NAD levels.

Autophagy is an essential catabolic process that promotes the clearance of surplus or damaged intracellular components. Loss of autophagy in age-related human pathologies contributes to tissue degeneration through a poorly understood mechanism. Here, we identify an evolutionarily conserved role of autophagy from yeast to humans in the preservation of nicotinamide adenine dinucleotide (NAD) levels, which are critical for cell survival. In respiring mouse fibroblasts with autophagy deficiency, loss of mitochondrial quality control was found to trigger hyperactivation of stress responses mediated by NADases of PARP and Sirtuin families. Uncontrolled depletion of the NAD(H) pool by these enzymes ultimately contributed to mitochondrial membrane depolarization and cell death. Pharmacological and genetic interventions targeting several key elements of this cascade improved the survival of autophagy-deficient yeast, mouse fibroblasts, and human neurons. Our study provides a mechanistic link between autophagy and NAD metabolism and identifies targets for interventions in human diseases associated with autophagic, lysosomal, and mitochondrial dysfunction.

Chronic altered light-dark cycle differentially affects hippocampal CA1 and DG neuronal arborization in diurnal and nocturnal rodents.

The hippocampus, an extension of the temporal part of the cerebral cortex, plays a crucial role in learning and memory. Structural and functional complexity within the hippocampus is greatly affected by a variety of external environmental stimuli including alteration in the light-dark (LD) cycle. The effect of altered LD cycle in learning and memory associated cognitive impairment has been reported in rodents. However, a comparative study of underlying neuronal changes between nocturnal and diurnal species is not well explored. The objective of the present study was to explore the morphological changes in hippocampal CA1 and DG neurons in response to prolonged constant condition viz. constant light (LL) and constant darkness (DD) in diurnal squirrels and nocturnal mice. Animals (n = 5/group) were placed in chronocubicle under 12:12 h LD, LL and DD. After four weeks, brain tissues were collected and processed for Golgi-Cox staining to analyze morphological changes in CA1 and DG neurons. The total and basal dendritic length, basal dendrite number, branch end, the diameter of apical dendrite and spine density were analyzed. The results showed a significant reduction in structural complexity of CA1 and DG neurons of squirrels exposed to prolonged constant darkness, whereas mice showed a significant increase as compared to LD. However, a significantly reduced neuronal complexity was observed in both squirrels and mice exposed to prolonged constant light. The results obtained were further confirmed by Sholl analysis of CA1 and DG neurons. The present study suggests that prolonged constant light may cause adverse effects on the neuronal complexity of both diurnal and nocturnal animals, but constant darkness may cause adverse effects mainly to the diurnal animals.

Crosstalk between epigenetics and mTOR as a gateway to new insights in pathophysiology and treatment of Alzheimer's disease.

Epigenetics in the current times has become a gateway to acquire answers to questions that were left unanswered by classical and modern genetics, be it resolving the complex mystery behind neurodegenerative disorders or understanding the complexity behind life-threatening cancers. It has presented to the world an entirely new dimension and has added a dynamic angle to an otherwise static field of genetics. Alzheimer's disease is one of the most prevalent neurodegenerative disorders is largely found to be a result of alterations in epigenetic pathways. These changes majorly comprise an imbalance in DNA methylation levels and altered acetylation and methylation of histones. They are often seen to cross-link with metabolic regulatory pathways such as that of mTOR, contributing significantly to the pathophysiology of AD. This review focusses on the study of the interplay of the mTOR regulatory pathway with that of epigenetic machinery that may elevate the rate of early diagnosis and prove to be a gateway to the development of an efficient and novel therapeutic strategy for the treatment of Alzheimer's disease at an early stage.

Differential response of diurnal and nocturnal mammals to prolonged altered light-dark cycle: a possible role of mood associated endocrine, inflammatory and antioxidant system.

The circadian system maintains internal 24 h oscillation of behavior and physiology, and its misalignment with external light-dark (LD) cycle results in negative health outcomes. In order to elucidate the effect of prolonged constant condition and the differences in the response between nocturnal and diurnal species, we studied the effects of constant light (LL) and constant darkness (DD) on a diurnal (squirrel) and a nocturnal (mouse) rodent species, focusing on the endocrine, inflammatory and antioxidant systems associated with depression-like behavior. Squirrels and mice (n = 10/group) were placed in chronocubicle under 12:12 h LD cycle, LL and DD. After 4 weeks, animals were subjected to sucrose preference test and blood and brain tissues were collected for measuring melatonin, corticosterone, proinflammatory cytokine, tumor necrosis factor-α (TNF-α) and the activity of primary antioxidant enzymes, catalase (CAT) and superoxide dismutase (SOD). The results show that in diurnal squirrels, prolonged constant darkness reduced sucrose preference, CAT, and SOD, increased corticosterone and TNF-α levels, but caused no significant change in the melatonin compared to LD condition. In contrast, in nocturnal mice constant darkness caused no significant changes in sucrose preference and corticosterone levels, increased melatonin, CAT and SOD levels but decreased TNF-α levels. Chronic LL caused a similar response in both squirrels and mice: it decreased sucrose preference, melatonin, CAT and SOD levels but increased corticosterone and TNF-α levels. Together, the study demonstrates differential effects of altered light-dark cycle in a diurnal and a nocturnal rodent on interrelated endocrine, inflammatory and antioxidant systems associated with depression-like behavior, with constant light having adverse effects on both species but constant darkness having a negative effect mainly in the diurnal squirrels.

Rare case of angiofibroma presenting as perineal hernia.

Angiofibroma is a benign soft tissue tumour presenting as a gradually progressive swelling in the vulvovaginal area in women and in the inguinoscrotal region in men. Being a rare tumour, there are only a few case reports in the literature, and among them, presentation as perineal herniation is very rare. En bloc resection of angiofibroma either via laparoscopic or open approach is the choice of treatment to avoid recurrence. Detailed pathological examination and immunohistochemistry workup are imperative to distinguish it from various mesenchymal tumours. Perineal hernia is itself rare and may occur spontaneously or following abdominoperineal resection, sacrectomy or pelvic exenteration. Surgical repair via open transabdominal and transperineal approaches has been described. Here, we report a case of a young woman who presented with spontaneous reducible perineal hernia with a soft tissue tumour as its content, which on histopathological investigation was found to be an angiofibroma.

Exocyst Subcomplex Functions in Autophagosome Biogenesis by Regulating Atg9 Trafficking.

During autophagy, double-membrane vesicles called autophagosomes capture and degrade the intracellular cargo. The de novo formation of autophagosomes requires several vesicle transport and membrane fusion events which are not completely understood. We studied the involvement of exocyst, an octameric tethering complex, which has a primary function in tethering post-Golgi secretory vesicles to plasma membrane, in autophagy. Our findings indicate that not all subunits of exocyst are involved in selective and general autophagy. We show that in the absence of autophagy specific subunits, autophagy arrest is accompanied by accumulation of incomplete autophagosome-like structures. In these mutants, impaired Atg9 trafficking leads to decreased delivery of membrane to the site of autophagosome biogenesis thereby impeding the elongation and completion of the autophagosomes. The subunits of exocyst, which are dispensable for autophagic function, do not associate with the autophagy specific subcomplex of exocyst.