Radical scavenging activity of Chlorophytum borivilianum L. root extract and its protective role in cauda epididymal sperm integrity in Mus musculus after gamma irradiation.

Background: Chlorophytum borivilianum L. is a recognized herbal medicine for the management of impotency in South Asian countries. In Ayurveda, it is used for the management of multiple health conditions, including diabetes, infection, and cardiovascular diseases. Parts of the plant have been used as excellent antioxidants and scavengers of free radicals. Since oxidative stress plays an important role in spermatogenesis and fertility in male populations, this study evaluated the role of ethanolic extract of C. borivilianum roots in epididymal sperm maturation against adversities posed by ionizing gamma irradiation. Materials and methods: Antioxidant potential of C. borivilianum root extract (CRE) was evaluated through DPPH (2,2-diphenylpicrylhydrazyl) and NO (nitric oxide) scavenging assays. Four groups of healthy Swiss albino mice were constituted, which were labeled as follows: Group I: sham control, Group II: 7-day pre-treatment with 50 mg/kg CRE, Group III: 6 Gy irradiation without pre-treatment, and Group IV: 7-day pre-treatment with 50 mg/kg CRE and 6 Gy irradiation on day 7. Swiss albino mice were observed for 30 days and later sacrificed to evaluate sperm quality parameters. Results: CRE showed a remarkable antioxidant potential with IC50 values of 46.37 µg/ml and 98.39 µg/ml for DPPH and NO, respectively. A significant decline (p < 0.001) in cauda epididymal sperm count, motility, and viability was observed in Group III animals. Group IV also showed a substantial decline (p < 0.01) in all three parameters compared to Group I; nonetheless, these were significantly higher than Group III. Morphological alterations indicated a coiled and bent tail, with the presence of cytoplasmic droplets in Group III, which declined substantially in Group IV. The ultrastructure of sperm indicated higher curvature of hook in Group III than Group IV, indicating specific interferences in the sperm maturation process. Conclusion: It was concluded that pre-treatment with 50 mg/kg body weight of CRE could protect sperm during epididymal maturation against oxidative stress.

Opposite response of blood vessels in the retina to 6° head-down tilt and long-duration microgravity.

The Spaceflight Associated Neuro-ocular Syndrome (SANS), associated with the headward fluid shifts incurred in microgravity during long-duration missions, remains a high-priority health and performance risk for human space exploration. To help characterize the pathophysiology of SANS, NASA's VESsel GENeration Analysis (VESGEN) software was used to map and quantify vascular adaptations in the retina before and after 70 days of bed rest at 6-degree Head-Down Tilt (HDT), a well-studied microgravity analog. Results were compared to the retinal vascular response of astronauts following 6-month missions to the International Space Station (ISS). By mixed effects modeling, the trends of vascular response were opposite. Vascular density decreased significantly in the 16 retinas of eight astronauts and in contrast, increased slightly in the ten retinas of five subjects after HDT (although with limited significance). The one astronaut retina diagnosed with SANS displayed the greatest vascular loss. Results suggest that microgravity is a major variable in the retinal mediation of fluid shifts that is not reproduced in this HDT bed rest model.

Vascular Patterning as Integrative Readout of Complex Molecular and Physiological Signaling by VESsel GENeration Analysis.

The molecular signaling cascades that regulate angiogenesis and microvascular remodeling are fundamental to normal development, healthy physiology, and pathologies such as inflammation and cancer. Yet quantifying such complex, fractally branching vascular patterns remains difficult. We review application of NASA's globally available, freely downloadable VESsel GENeration (VESGEN) Analysis software to numerous examples of 2D vascular trees, networks, and tree-network composites. Upon input of a binary vascular image, automated output includes informative vascular maps and quantification of parameters such as tortuosity, fractal dimension, vessel diameter, area, length, number, and branch point. Previous research has demonstrated that cytokines and therapeutics such as vascular endothelial growth factor, basic fibroblast growth factor (fibroblast growth factor-2), transforming growth factor-beta-1, and steroid triamcinolone acetonide specify unique "fingerprint" or "biomarker" vascular patterns that integrate dominant signaling with physiological response. In vivo experimental examples described here include vascular response to keratinocyte growth factor, a novel vessel tortuosity factor; angiogenic inhibition in humanized tumor xenografts by the anti-angiogenesis drug leronlimab; intestinal vascular inflammation with probiotic protection by Saccharomyces boulardii, and a workflow programming of vascular architecture for 3D bioprinting of regenerative tissues from 2D images. Microvascular remodeling in the human retina is described for astronaut risks in microgravity, vessel tortuosity in diabetic retinopathy, and venous occlusive disease.

Differential Activity of Antioxidants in Testicular Tissues Following Administration of Chlorophytum borivilianum in Gamma-Irradiated Swiss Albino Mice.

Background: Oxidative stress induced by radiation causes variable expression of antioxidant enzymes in a tissue-specific manner. Testicular tissues carry out the complex process of spermatogenesis, and studies indicate that testicular damages due to irradiation require long-term recovery before complete resumption. Ionizing radiation also causes oxidative stress in tissues, leading to testicular damage. Aims and Objectives: This study measured differential expression of antioxidant enzymes following administration of C. borivilianum root extract (CRB) in response to irradiation-induced oxidative stress. The activity of various important endogenous enzymatic defense systems was evaluated and correlated for strength of association. Materials and method: Two forms of C. borivilianum (CB) extracts [CB alone and CB-silver nanoparticles (AgNPs)] were administered at a dose of 50 mg/kg body weight to Swiss albino male mice for 7 consecutive days. After that, they were irradiated with 6 Gy irradiation and further used to study various parameters of antioxidant enzymes. Results: Results indicate a significant increase in the level of glutathione (GSH) and the activity of GSH-related antioxidant enzymes in irradiated mice treated with CRE and CRE-AgNPs (silver nanoparticles biosynthesized using C. borivilianum root extract) in comparison to non-pretreated ones (groups I and II). Reciprocal elevation was observed in related enzymes, that is, glutathione S-transferase activity (GST), glutathione reductase (GR), and glutathione peroxidase activity (GPx). Elevation in the activity of catalase (CAT) and superoxide dismutase (SOD) was also evident in both the irradiated groups pretreated with CRE-AgNPs. However, expression of CAT in the CRE-treated irradiated group was similar to that of the non-treated irradiated group. Higher association among CAT-SOD, CAT-GPx, and GR-GST was observed. Conclusion: Overall, it was observed that testicular cells post-irradiation in all groups go through intense oxidative stress; however, groups pretreated with CRE or CRE-AgNPs indicated better toleration and resumption of antioxidant capacity. CRE or CRE-AgNPs pretreated non-irradiated groups mostly remained within the control range indicating stimulated expression of antioxidants.

Decreased Vascular Patterning in the Retinas of Astronaut Crew Members as New Measure of Ocular Damage in Spaceflight-Associated Neuro-ocular Syndrome.

Purpose: Ocular structural and functional changes, collectively termed spaceflight-associated neuro-ocular syndrome (SANS), have been described in astronauts undergoing long-duration missions in the microgravity environment of the International Space Station. We tested the hypothesis that retinal vascular remodeling, particularly by smaller vessels, mediates the chronic headward fluid shifts associated with SANS. Methods: As a retrospective study, arterial and venous patterns extracted from 30° infrared Heidelberg Spectralis retinal images of eight crew members acquired before and after six-month missions were analyzed with NASA's recently released VESsel GENeration Analysis (VESGEN) software. Output parameters included the fractal dimension and overall vessel length density that was further classified into large and small vascular branching generations. Vascular results were compared with SANS-associated clinical ocular measures. Results: Significant postflight decreases in Df, Lv, and in smaller but not larger vessels were quantified in 11 of 16 retinas for arteries and veins (P value for Df, Lv, and smaller vessels in all 16 retinas were ≤0.033). The greatest vascular decreases occurred in the only retina displaying clinical evidence of SANS by choroidal folds and optic disc edema. In the remaining 15 retinas, decreases in vascular density from Df and Lv ranged from minimal to high by a custom Subclinical Vascular Pathology Index. Conclusions: Together with VESGEN, the Subclinical Vascular Pathology Index may represent a new, useful SANS biomarker for advancing the understanding of SANS etiology and developing successful countermeasures for long duration space exploration in microgravity, although further research is required to better characterize retinal microvascular adaptations.

Effects of Chlorophytum borivilianum Sant. F against gamma radiation-induced testicular injuries in Swiss albino mice.

BACKGROUND: Radiation therapy is considered as an important tool in cancer treatment. Despite its impressive role in treating cancer, severe side effects in organs have been reported. To address these therapeutic side effects, several combination methods have been identified to minimize adverse effects caused by radiation therapy. AIMS AND OBJECTIVES: Based on higher radioactive sensitivity of testicular tissues, administration of Chlorophytum borivilianum (CB) Sant. F extracts was evaluated for its protective effects against radiation in testis. MATERIALS AND METHODS: Two forms of CB extracts (CB alone and CB-silver nanoparticles [AgNPs]) were administered at a dose of 50 mg/kg body weight in Swiss albino male mice for 7 consecutive days. Following 6 Gy gamma radiation, animals were observed for 30 days in four phases. Sperm counts, body weight, testicular weight and stereological and histological evaluation of testis were evaluated. RESULTS: Following irradiation, a significant decline in body weight (P = 0.008) and testicular weight (P = 0.001) was noted when compared with control. Ununiformed type A and B spermatogonia, partially filled tubules, inter-tubular vacuoles, and disrupted epithelium were the main types of damages caused by irradiation. Reorganization and resumption of histological features emerged from the 15th day postirradiation in CB extract (CBE)-treated animals. CONCLUSION: Testicular response was observed against radiation in animals treated with CB extracts, while CB-AgNPs indicated better toleration when compared to CB extract alone.

Loss of Angiotensin-Converting Enzyme 2 Exacerbates Diabetic Retinopathy by Promoting Bone Marrow Dysfunction.

Angiotensin-converting enzyme 2 (ACE2) is the primary enzyme of the vasoprotective axis of the renin angiotensin system (RAS). We tested the hypothesis that loss of ACE2 would exacerbate diabetic retinopathy by promoting bone marrow dysfunction. ACE2-/y were crossed with Akita mice, a model of type 1 diabetes. When comparing the bone marrow of the ACE2-/y -Akita mice to that of Akita mice, we observed a reduction of both short-term and long-term repopulating hematopoietic stem cells, a shift of hematopoiesis toward myelopoiesis, and an impairment of lineage- c-kit+ hematopoietic stem/progenitor cell (HS/PC) migration and proliferation. Migratory and proliferative dysfunction of these cells was corrected by exposure to angiotensin-1-7 (Ang-1-7), the protective peptide generated by ACE2. Over the duration of diabetes examined, ACE2 deficiency led to progressive reduction in electrical responses assessed by electroretinography and to increases in neural infarcts observed by fundus photography. Compared with Akita mice, ACE2-/y -Akita at 9-months of diabetes showed an increased number of acellular capillaries indicative of more severe diabetic retinopathy. In diabetic and control human subjects, CD34+ cells, a key bone marrow HS/PC population, were assessed for changes in mRNA levels for MAS, the receptor for Ang-1-7. Levels were highest in CD34+ cells from diabetics without retinopathy. Higher serum Ang-1-7 levels predicted protection from development of retinopathy in diabetics. Treatment with Ang-1-7 or alamandine restored the impaired migration function of CD34+ cells from subjects with retinopathy. These data support that activation of the protective RAS within HS/PCs may represents a therapeutic strategy for prevention of diabetic retinopathy. Stem Cells 2018;36:1430-1440.

RNA interference technology with emphasis on delivery vehicles-prospects and limitations.

CONTEXT: RNA interference (RNAi)-based therapeutics rely upon safe and efficient delivery of small interfering RNA (siRNA) molecules. OBJECTIVE: This review explores various dimensions of RNAi with emphasis on the development of nanoparticle-based delivery vectors for safe and efficient siRNA delivery. METHODS: An exhaustive database search has been done regarding studies done to investigate the potential of siRNA delivery employing nanoparticles has been cited in the present review. RESULTS AND CONCLUSION: With the current challenges, there is a need for collaborative work allowing for the successful development of nanoparticle/siRNA complexes as health-promoting biotherapeutics.