Protective effect of dental pulp stem cells' conditioned medium against cisplatin-induced testicular damage in rats.

Cisplatin is a highly effective chemotherapy drug used to treat most solid tumors. However, one of its side effects is testicular toxicity, which can lead to fertility abnormalities. This study investigated the effectiveness of dental pulp mesenchymal stem cells conditioned medium (DPSC-CM) on cisplatin-induced testicular toxicity. In this study, 36 eight-week-old male Wistar rats were randomly divided into three groups equally (n = 12). Group 1 control "CTR", which received normal saline (0.5 ml) intraperitoneally (i.p), group 2 "Cis" which received an intraperitoneal dose of cisplatin (7 mg/kg), and group 3 "Cis+CM" which received an i.p injection of DPSC-CM (0.5 mg/kg) after cisplatin injection. Biochemical, histomorphometric, and histopathological studies were performed on the testis. Our results exhibited that cis administration led to a decline in total body weight, testis weight, diameter, and volume. A decrease in testosterone and IL-6 serum levels, as well as a decrease in IL-6 and TNFα levels, the activity of catalase and SOD enzymes, and an increase in MDA in testicular tissue were detected. Testicular tissue damage was associated with a significant decrease in tube diameter, germinal epithelium height, number of spermatogonia and Sertoli cells, along with a noticeable increase in basement membrane thickness, and perivascular fibrosis. DMSC-CM improved all the mentioned parameters. Taken together, our results demonstrated that DMSC-CM due to its antioxidant and anti-inflammatory properties, could be effective in reversing cisplatin-induced testicular toxicity.

The effects of induced type I diabetes on developmental regulation of GDNF, NRTN, and NCAM proteins in the dentate gyrus of male rat offspring.

BACKGROUND: Maternal diabetes during pregnancy can affect the neurological development of offspring. Glial cell-derived neurotrophic factor (GDNF), neurturin (NRTN), and neural cell adhesion molecules (NCAM) are three important proteins for brain development. Therefore, this study aimed to investigate the impacts of the mentioned neurotrophic factors in the hippocampal dentate gyrus (DG) of rat offspring born to diabetic mothers. METHODS: Wistar female rats were randomly allocated into diabetic (STZ-D) [(45 mg/kg BW, STZ (Streptozotocin), i.p)], diabetic + NPH insulin (STZ-INS) [(4-6 unit/kg/day SC)], and control groups. The animals in all groups were mated by non-diabetic male rats. Two weeks after birth, male pups from each group were sacrificed and then protein contents of GDNF, NRTN, and NCAM were evaluated using immunohistochemistry. RESULTS: The study found that the expression of GDNF and NRTN in the hippocampus of diabetic rat offspring was significantly higher compared to the diabetic+ insulin and control groups, respectively (P < 0.01, P < 0.001). Additionally, the expression of NCAM was significantly higher in the diabetic group the diabetic+ insulin and control groups (P < 0.01, P < 0.001). CONCLUSIONS: The results of the study revealed that diabetes during pregnancy significantly impacts the distribution pattern of GDNF, NRTN, and NCAM in the hippocampus of rat neonates.

Clinical Correlation of Altered Molecular Signatures in Epileptic Human Hippocampus and Amygdala.

Widespread alterations in the expression of various genes could contribute to the pathogenesis of epilepsy. The expression levels of various genes, including major inhibitory and excitatory receptors, ion channels, cell type-specific markers, and excitatory amino acid transporters, were assessed and compared between the human epileptic hippocampus and amygdala, and findings from autopsy controls. Moreover, the potential correlation between molecular alterations in epileptic brain tissues and the clinical characteristics of patients undergoing epilepsy surgery was evaluated. Our findings revealed significant and complex changes in the expression of several key regulatory genes in both the hippocampus and amygdala of patients with intractable epilepsy. The expression changes in various genes differed considerably between the epileptic hippocampus and amygdala. Different correlation patterns were observed between changes in gene expression and clinical characteristics, depending on whether the patients were considered as a whole or were subdivided. Altered molecular signatures in different groups of epileptic patients, defined within a given category, could be viewed as diagnostic biomarkers. Distinct patterns of molecular changes that distinguish these groups from each other appear to be associated with epilepsy-specific functional consequences.

Crystal structure and supra-molecular features of a bis-urea-functionalized pillar[5]arene.

The crystal structure of a bis-urea derivative based on A1/A2-functionalized pillar[5]arene (DUP) that encapsulates dimethyl formamide (DMF) inside the macrocyclic cavity is reported. The crystal structure of DUP·DMF, C63H70N4O12·C3H7NO, reveals that out of two urea functionalized spacers, one arm is oriented above the macrocyclic cavity with strong hydrogen-bonding inter-actions between the urea H atoms and DMF guest, whereas, the other arm is positioned away from the macrocycle, leading to inter-molecular hydrogen-bonding inter-actions between the urea H atoms of two adjacent pillar[5]arene macrocycles, resulting in the formation of a supra-molecular dimer.

The effects of vitamin D on cardiovascular damage induced by lipopolysaccharides in rats.

Introduction: Inflammation and oxidative stress are contributed to cardiovascular diseases. Vitamin D (Vit D) has antioxidant and anti-inflammatory properties. In the current research, the effect of Vit D on cardiac fibrosis and inflammation, and oxidative stress indicators in cardiovascular tissues was studied in lipopolysaccharides(LPS) injected rats. Methods: Rats were distributed into 5 groups and were treated for 2 weeks. Control: received vehicle(saline supplemented with tween-80) instead of Vit D and saline instead of LPS, LPS: treated by 1 mg/kg of LPS and was given vehicle instead of Vit D, LPS-Vit D groups: received 3 doses of Vit D (100, 1000, and 10000 IU/kg) of Vit D in addition to LPS. Vit D was dissolved in saline supplemented with tween-80 (final concentration 0.1%) and LPS was dissolved in saline. The white blood cell (WBC) was counted. Oxidative stress markers were determined in serum, aorta, and heart. Cardiac tissue fibrosis was also estimated using Masson's trichrome staining method. Results: WBC and malondialdehyde (MDA) were higher in the LPS group than the control group, whereas the thiol content, superoxide dismutase (SOD), and catalase (CAT) were lower in the LPS group than the control group (P<0.01 and P<0.001). Administration of Vit D decreased WBC (P<0.001) and MDA (P<0.05 and P<0.001) while enhanced thiol (dose 10000 IU/Kg) (P<0.001), SOD (dose 10000 IU/kg) (P<0.001), and CAT (P<0.05 and P<0.001) compared to the LPS group. All doses of Vit D also decreased cardiac fibrosis compared to the LPS group (P<0.001). Conclusion: Vit D protected the cardiovascular against the detrimental effect of LPS. This cardiovascular protection can be attributed to the antioxidant and anti-inflammatory properties of Vit D.

Vitamin D alleviates hypothyroidism associated liver dysfunction: Histological and biochemical evidence.

There is a complex correlation between thyroid hormones (THs) and liver function. Hypothyroidism as a failure of the thyroid gland to produce adequate thyroid hormones to fulfill the metabolic requirements of the body, may perturb liver structure and function. Emerging evidence suggests the protective effects of vitamin D against liver damage. Herein, this study aimed to investigate the role of vitamin D in hypothyroidism-associated liver injury. Forty male Wistar rats were classified into 4 groups: control, hypothyroid (Hypo) group received 0.05% PTU, Hypo- Vitamin D groups were given 100 and 500 IU/kg vitamin D orally via gavage for 6 weeks. Serum level of liver function including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were measured. Malondialdehyde (MDA) level, superoxide dismutase (SOD) enzyme activity, and total thiol content were measured as oxidative stress indicators in the liver tissue. Furthermore, to estimate liver tissue fibrosis, Masson's trichrome staining was done. Our findings showed that hypothyroidism-induced liver fibrosis was associated with increased levels of ALT, AST and ALP. Though, vitamin D administration could significantly reduce the ALT, AST and ALP in the serum and suppress the accumulation of collagen fibers. Moreover, the activity of SOD and total thiol content was notably reduced, while the MDA content was significantly increased in the PTU- induced hypothyroid rats compared to the control group. Nonetheless, treatment with vitamin D improved mentioned oxidative stress markers in the Hypo-vitamin D groups. In conclusion, vitamin D due to its potential antioxidant and anti-fibrotic properties could be effective in the decrease of hypothyroidism-associated liver injury.

We have Neglected "Ourselves"; A Qualitative Study on Iranian Parents of Children with Aphakia.

Background: Contact lenses play a substantial role in the management of childhood aphakia. However, the use and care of the lenses can be challenging. Despite its prevalence, the phenomenon of living with children with aphakia is not explained in Iran yet. The aim of this study was to illuminate the lived experience of the parents of children with aphakia. Materials and Methods: This hermeneutic phenomenological study was conducted on the parents who have been referred to Farabi Eye Hospital of Tehran, Iran in 2019, whose children were diagnosed with aphakia, and the condition was corrected with contact lenses. Qualitative semi-structured interviews were conducted with 20 parents of children with congenital cataract. Analysis was based on the framework of Diekelmann enabled data interpretation and elaboration of shared themes. Results: The 20 parents involved in the study consisted of 12 women and 8 men. The participant's experiences were classified in 4 categories: Self-Ignorance, Troubled mind, Self-Regulation, and Coping with the problem while hoping for the future. Conclusions: "Self-Ignorance" and "Troubled Mind" indicates that because of the risk of burnout in the long-term process of treatment, the psychological support of parents is necessary. Psychological support will continue until the parents acquire the ability of self-regulation. Giving a realistic hope to families is a core element in psychological support.

An application of social marketing for promoting HIV testing in Iran.

BACKGROUND: It has been estimated that 60,000 Iranians have been infected with HIV/AIDS and only 36% of them are aware of their status. This study aimed to design, implement and evaluate a social marketing campaign to promote HIV testing in Boyer-Ahmad County, Kohgiluyeh, and Boyer-Ahmad Province, southwest of Iran. MATERIALS AND METHODS: This study was a quasi-experimental pretest-posttest without a control group, developed based on a social marketing assessment and response tool. To design the intervention formative research was conducted, comprised of four focus group discussion sessions with 42 participants of the target community along with seven in-depth semi-structured personal interviews with health care providers involved in the HIV/AIDS Program. Data analysis was done manually using content analysis and the main content was formulated for the campaign. Afterward, the slogan and messages of the campaign were developed. The campaign's materials including banners, posters, pamphlets, referral forms, and short messages were designed, pretested, and revised. Ultimately, the campaign was conducted for one month in October 2019. To determine the effectiveness of the campaign, the rate of referrals to the Center for Behavioral Health Counseling Services (CBHCS), for three months before and after the campaign, was compared. RESULTS: Qualitative findings identified that the majority of the interviewees mentioned that the main reasons for the low rate of referrals to get tested for HIV were lack of awareness and information about HIV/AIDS and its diagnosis as well as the free and confidential tests available from the CBHCS. Moreover, the stigma associated with HIV/AIDS was another important reason for low referrals for testing. The rate of referrals for HIV testing in the three months leading up to the campaign was 18, 32, and 23 people, and three months after the campaign was 64, 81, and 44 individuals; respectively. The results of the multivariate analysis demonstrated that the campaign had increased the rates of referrals for HIV testing through its significant influence on females, and individuals with academic degrees. CONCLUSION: It can be concluded that the social marketing campaign was successful in persuading people to get tested for HIV.

Spatially Designed Supramolecular Anion Receptors Based on Pillar[5]arene Scaffolds: Synthesis and Halide Anion Binding Properties.

Urea-functionalized anion receptors based on brominated functionalized pillar[5]arenes were prepared. The binding affinity toward halide anions was investigated and probed using 1H NMR titration and isothermal titration calorimetry (ITC). The complexation behavior was affected by the structure of the receptor and the nature of the anionic guest. The synthesized receptors are highly selective toward fluoride resulting in the formation of a 1:2 host-to-guest complex. The anion receptor based on the 1,3-alternate pillar[5]arene regioisomer shows the highest affinity toward fluorine anions. No significant interactions were observed with larger bromine anions. The formation of a self-assembled supramolecular polymer driven by hydrogen bonds in solution was demonstrated by diffusion-ordered spectroscopy (DOSY), ITC, and dynamic light scattering (DLS) measurements. From ITC dilution experiments, we found that the supramolecular polymer self-assembly at higher concentrations is a spontaneous process as indicated by the positive value of Gibbs free energy (ΔG = 12.04 kJ mol-1).

Anti-apoptotic and neurogenic properties in the hippocampus as possible mechanisms for learning and memory improving impacts of vitamin D in hypothyroid rats during the growth period.

The current study was designed to investigate the protective effects of Vitamin D (VD) on hippocampal neurogenesis, apoptosis, and subsequent hippocampal-dependent learning and memory performance in hypothyroid juvenile rats. Twenty eight male Wistar rats were randomly divided into four groups as; control, Hypothyroid (Hypo), Hypo-VD100 and Hypo-VD500. Hypothyroidism was induced by giving 0.05 % propylthiouracil (PTU), and VD (100 or 500 IU/kg) treatment was performed daily by gavage. At the end of treatment, Morris water maze (MWM) was carried out and evaluated hippocampal neurogenesis, apoptosis, and dark neurons (DNs). Our results revealed that the escape latency and the traveled distance to find the platform in the Hypo group were significantly longer but the time spent and distance traveled in the target area in probe trial was lower than the control group. Hypothyroidism was accompanied by a marked decrease in hippocampal neurogenesis, and a significant increase in the number of apoptotic neurons and DNs compared to the control group. VD decreased escape latency and the traveled distance to find the platform but increased the time spent and distance traveled in the target area in probe trial than the Hypo group. VD also increased neurogenesis, reduced apoptosis and DNs production compared to the Hypo group. In conclusion, these results support a role for VD in the restoring hippocampal neurogenesis impairment, reducing neuronal apoptosis, and DNs in hypothyroid rats as well as raise the possibility that VD may contribute as a therapeutic approach to improve the learning and memory deficits associated with hypothyroidism.

Leveraging machine learning for taxonomic classification of emerging astroviruses.

Astroviruses are a family of genetically diverse viruses associated with disease in humans and birds with significant health effects and economic burdens. Astrovirus taxonomic classification includes two genera, Avastrovirus and Mamastrovirus. However, with next-generation sequencing, broader interspecies transmission has been observed necessitating a reexamination of the current host-based taxonomic classification approach. In this study, a novel taxonomic classification method is presented for emergent and as yet unclassified astroviruses, based on whole genome sequence k-mer composition in addition to host information. An optional component responsible for identifying recombinant sequences was added to the method's pipeline, to counteract the impact of genetic recombination on viral classification. The proposed three-pronged classification method consists of a supervised machine learning method, an unsupervised machine learning method, and the consideration of host species. Using this three-pronged approach, we propose genus labels for 191 as yet unclassified astrovirus genomes. Genus labels are also suggested for an additional eight as yet unclassified astrovirus genomes for which incompatibility was observed with the host species, suggesting cross-species infection. Lastly, our machine learning-based approach augmented by a principal component analysis (PCA) analysis provides evidence supporting the hypothesis of the existence of human astrovirus (HAstV) subgenus of the genus Mamastrovirus, and a goose astrovirus (GoAstV) subgenus of the genus Avastrovirus. Overall, this multipronged machine learning approach provides a fast, reliable, and scalable prediction method of taxonomic labels, able to keep pace with emerging viruses and the exponential increase in the output of modern genome sequencing technologies.

Neuroprotective effects of the fractions of Ocimum basilicum in seizures induced by pentylenetetrazole in mice.

Objective: Neuroprotective and antioxidant effects of Ocimum basilicum (O. basilicum) against pentylenetetrazole (PTZ)-induced seizures were investigated. Materials and Methods: Mice were divided as follows: (Group 1) Control, (Group 2) PTZ, (Groups 3-5) 50,100 and 200 mg/kg hydro-ethanolic (HE) extract, and (Groups 6-8) 200 mg/kg ethyl-acetate (EAF), N-hexane (NHF) and water (WF) fractions. Minimal clonic seizures (MCS) and generalized tonic-clonic seizures (GTCS) latencies were measured. Biochemical and histological studies were done. Results: MCS and GTCS latency in HE groups were longer than the PTZ group (p<0.05 to p<0.001). EAF and NHF prolonged the onset of MCS and GTCS (p<0.001). PTZ increased malondialdehyde (MDA) and dark neuron (DN) production while decreased thiol, catalase (CAT) and superoxide dismutase (SOD) (p<0.05 to p<0.001). Pre-treatment by HE and all fractions of the plant attenuated MDA and DN while increased thiol, CAT and SOD (p<0.01 to p<0.001). Conclusion: EAF and NHF had anticonvulsant properties. The extract and fractions protected the brain from PTZ-induced oxidative damages and showed neuroprotective effects.

Evaluation of sperm chromatin/DNA integrity, morphology, and Catsper expression on diabetic C57BL/6 mice.

BACKGROUND: Diabetes is associated with reproductive impairment on the male reproductive system and causes complications such as decreased libido, fertility, spermatogenesis, sperm motility, and morphology. High levels of blood sugar may affect sperm quality and reduce the potential for male fertility. Increased levels of sperm DNA damage is often associated with reduced count and motility or abnormal morphology. METHODS: This experimental study was conducted in Mashhad University of Medical Sciences. In this work, 40 mice (C57BL/6) were divided randomly into 4 groups: 1) Control, 2) Diabetic, 3) Diabetic + Insulin, and 4) Sham. After 35 days, the right epididymis of all specimens was used for Real-Time PCR and left epididymis for evaluation of sperm parameters using Aniline blue, Toluidine blue, Papanicolaou, and immunohistochemical study. Also, testes were applied for immunohistochemical, TUNEL studies, and biochemical assay. RESULTS: Results of this study showed that chromatin integrity, morphology, cation channels of sperm (Catsper) expression, and biochemical factors level were significantly changed in diabetic mice in comparison to other groups (P<0.05) and treatment with insulin improved these parameters. CONCLUSION: Our findings showed that the sperm parameters such as DNA integrity, morphology, and Catsper expression change in diabetic mice.

The balanced scorecard as a strategic management tool in hospital pharmacies: an experimental study.

PURPOSE: A balanced scorecard (BSC) is an applied tool for implementing strategic management in various organizations. Implementing strategic management using the BSC approach has not received much attention in pharmacy departments. This study aims to provide a model for the strategic management of pharmacy departments using the BSC framework. DESIGN/METHODOLOGY/APPROACH: This experimental study was conducted from 2015 to 2018 in a 300-bed hospital and regional healthcare centers affiliated with the Petroleum Industry Health Organization in Tehran province, Iran. After carefully reviewing the organization's mission and vision, the strategic objectives were determined via the internal matrix and the external matrix (IE matrix), and the strengths-weaknesses-opportunities-threats matrix (SWOT matrix) were examined. Then, six BSC measures and interventions were identified, and each was examined from the perspectives of finance, patient satisfaction, internal processes and learning/growth. Finally, the proposed strategy was evaluated. FINDINGS: Results showed significant increases in patient satisfaction and gross profit. The observed increase range, from 0.09 to 0.29, indicates more effective operational management for optimal resource utilization. In addition, the pharmacy department was able to save US $539,137 by implementing prepared protocols for expensive medications. Similarly, the pharmacy department saved $442,899 during the two years of our strategic management plan by implementing the standard mechanism for returning unused medications to the pharmacy department after patients were discharged from various treatment units. ORIGINALITY/VALUE: This study is among the first studies to demonstrate the simultaneous development, implementation and evaluation of the proposed strategy using the BSC in a pharmacy department in a public healthcare center. The BSC application improved the optimal use of resources and reduced costs while increasing patient satisfaction. It appears that the application of such an intervention may be as valuable to public pharmacies as it is to other private centers.

The protective effect of co-administration of platelet-rich plasma (PRP) and pentoxifylline (PTX) on cyclophosphamide-induced premature ovarian failure in mature and immature rats.

Cyclophosphamide (CP), as an antineoplastic agent, causes premature ovarian failure (POF) due to ovarian toxicity and subsequent infertility in women. Platelet-rich plasma (PRP) has accumulated significant attention in regenerative medicine. Pentoxifylline (PTX) as a methylxanthine derivative has been shown to have antioxidant and antiapoptotic properties. The aim of this study was to evaluate the protective effect of PRP and PTX on CP-induced POF. Fifty mature and immature female rats were assigned into five groups: control, CP (75 mg/kg, intraperitoneal [ip] on days 1 and 10 to induce POF), CP + PRP (200 µl, ip, half an hour after CP injection on day 1 and 10), CP + PTX (50 mg/kg, orally, half an hour after CP injection daily for 21 day), and CP + PRP + PTX. At the end of experiments on day 21, measurement of body weight, ovarian parameters (ovarian volume, follicular granulosa cell layers diameter, oocyte diameter, and the number of granulosa cells), measurement of ovarian hormone in sera for estradiol (E2), and anti-Mullerian hormone (AMH), as well as biochemical assessment were performed.The results showed that CP significantly reduced the ovarian parameters, E2, AMH, superoxide dismutase (SOD) activity and increased Malondialdehyde (MDA) levels compared to the control group (p < 0.001). Our results also indicated that all histomorphometric parameters and biochemical markers in CP-induced POF, were preserved close to normal by PRP and PTX treatments in both mature and immature rats (p < 0.001). Therefore, it is concluded that the co-administration of PRP and PTX can protect the ovary from CP-induced POF.

The association between micronutrients and the SARS-CoV-2-specific antibodies in convalescent patients.

BACKGROUND: Various micronutrients play key roles in the immune responses to viral infection, antibody synthesis, and susceptibility to infection. This study aimed to investigate the role of micronutrients on the immune responses following SARS-CoV-2 infection. METHODS: To evaluate humoral immunity following SARS-CoV-2 infection, the levels of SARS-CoV-2-specific IgM and IgG, as well as the concentrations of different micronutrients, were determined in 36 convalescent COVID-19 patients 60 days after infection. Furthermore, the correlation between biochemical and hematological parameters, clinical features, and the changes in adiposity with SARS-CoV-2 antibodies was evaluated. RESULTS: Serum IgM and IgG antibodies were detected in 38.8% and 83.3% of recovered patients after 60 days of COVID-19 infection, respectively. The values of SARS-CoV-2-specific IgG were negatively correlated with the number of the platelet. Moreover, the values of SARS-CoV-2-specific IgM were positively correlated with LDH and the vitamin B12 concentration. Furthermore, a gender-specific association of SARS-CoV-2-specific IgG and IgM with vitamins D as well as with B9 and zinc was observed. A significant negative correlation was observed between the values of IgG with vitamin D in male participants and a positive correlation was detected between IgG values and B9 in female participants. Moreover, IgM levels with serum zinc values in females were negatively correlated. CONCLUSION: Our study suggests the potential role of micronutrients in gender-specific humoral immunity following SARS-CoV-2 infection. Further studies are required with a greater sample of subjects to substantiate the validity and robustness of our findings.

The effects of vitamin D on learning and memory of hypothyroid juvenile rats and brain tissue acetylcholinesterase activity and oxidative stress indicators.

Apart from a role as a key regulator of calcium/phosphate homeostasis, vitamin D (Vit D) is suggested to be a potential player in nervous system growth and function. This study aimed to assess the impacts of Vit D administration on memory impairment, oxidative damage, and acetylcholinesterase (AchE) overactivity in hypothyroid juvenile rats. The animals were randomly grouped as (1) Control; (2) Hypothyroid; (3) Hypothyroid-Vit D100, and (4) Hypothyroid-Vit D 500. Propylthiouracil (PTU) was added to their drinking water (0.05%) for 6 weeks, and Vit D (100 or 500 IU/kg) treatment was performed daily by gavage. Morris water maze (MWM) and passive avoidance (PA) tests were performed. The brains were removed under deep anesthesia, then the hippocampal and cortical tissues were separated to assess biochemical parameters. Hypothyroidism was significantly associated with learning and memory impairment in MWM and PA tests. Hypothyroidism was also accompanied by an elevation in AChE activity and malondialdehyde (MDA) content and a reduced level of thiol content and superoxide dismutase (SOD) activity in the brain. Treatment with Vit D recovered hypothyroidism-induced cognitive impairment and improved memory performance in MWM and PA tasks. On the other hand, Vit D alleviated AChE activity and MDA level, whereas increased SOD activity and thiol content in the hippocampal and cortical tissues. In conclusion, these outcomes suggest an association between the oral administrations of Vit D and learning and memory improvement of hypothyroid rats, which was accompanied by decreasing AChE activity and brain tissue oxidative damage.

DeLUCS: Deep learning for unsupervised clustering of DNA sequences.

We present a novel Deep Learning method for the Unsupervised Clustering of DNA Sequences (DeLUCS) that does not require sequence alignment, sequence homology, or (taxonomic) identifiers. DeLUCS uses Frequency Chaos Game Representations (FCGR) of primary DNA sequences, and generates "mimic" sequence FCGRs to self-learn data patterns (genomic signatures) through the optimization of multiple neural networks. A majority voting scheme is then used to determine the final cluster assignment for each sequence. The clusters learned by DeLUCS match true taxonomic groups for large and diverse datasets, with accuracies ranging from 77% to 100%: 2,500 complete vertebrate mitochondrial genomes, at taxonomic levels from sub-phylum to genera; 3,200 randomly selected 400 kbp-long bacterial genome segments, into clusters corresponding to bacterial families; three viral genome and gene datasets, averaging 1,300 sequences each, into clusters corresponding to virus subtypes. DeLUCS significantly outperforms two classic clustering methods (K-means++ and Gaussian Mixture Models) for unlabelled data, by as much as 47%. DeLUCS is highly effective, it is able to cluster datasets of unlabelled primary DNA sequences totalling over 1 billion bp of data, and it bypasses common limitations to classification resulting from the lack of sequence homology, variation in sequence length, and the absence or instability of sequence annotations and taxonomic identifiers. Thus, DeLUCS offers fast and accurate DNA sequence clustering for previously intractable datasets.

DUBStepR is a scalable correlation-based feature selection method for accurately clustering single-cell data.

Feature selection (marker gene selection) is widely believed to improve clustering accuracy, and is thus a key component of single cell clustering pipelines. Existing feature selection methods perform inconsistently across datasets, occasionally even resulting in poorer clustering accuracy than without feature selection. Moreover, existing methods ignore information contained in gene-gene correlations. Here, we introduce DUBStepR (Determining the Underlying Basis using Stepwise Regression), a feature selection algorithm that leverages gene-gene correlations with a novel measure of inhomogeneity in feature space, termed the Density Index (DI). Despite selecting a relatively small number of genes, DUBStepR substantially outperformed existing single-cell feature selection methods across diverse clustering benchmarks. Additionally, DUBStepR was the only method to robustly deconvolve T and NK heterogeneity by identifying disease-associated common and rare cell types and subtypes in PBMCs from rheumatoid arthritis patients. DUBStepR is scalable to over a million cells, and can be straightforwardly applied to other data types such as single-cell ATAC-seq. We propose DUBStepR as a general-purpose feature selection solution for accurately clustering single-cell data.

Hepatoprotective Impact of Ghrelin against Cyclophosphamide-Induced Toxicity in the Male Mice.

BACKGROUND: Despite its vast spectrum of clinical usage, cyclophosphamide (CP) exerts many adverse impacts, including hepatotoxicity. Antioxidant properties of ghrelin might protect the liver from CP-induced toxicity. The current study aimed to assess the protective impacts of ghrelin on CP-induced liver toxicity. METHODS: Forty male mice were randomly divided into four groups (n=10) Group 1 as control received no intervention,group 2 received cyclophosphamide (CP) (100 mg/kg, i.p.) for five weeks and once a week. Group 3 received CP+ghrelin (CP+G), (80 µg/kg daily, i.p.) for five weeks. Group 4 received ghrelin with above-mentioned dose. At the end of the experiment, the mice were sacrificed to remove liver tissuesfor histological and biochemical examination. RESULTS: Malondialdehyde (MDA) level increased after CP treatment but ghrelin administration significantly decreased the level of MDA (P<0.05). Measurement of the total antioxidant capacity (TAC) noted a significant decrease in the CP group against the control group (P<0.05). Ghrelin treatment in the CP+G group considerably increased the TAC activity when compared to the CP group (P<0.05). Histological examinations also confirmed the hepatocyte necrosis, local bleeding and inflammation, vacuolation, and sinusoidal dilation in the CP group, ghrelin administration reduced the destructive effects of CP on the liver significantly (P<0.05). CONCLUSION: Our results reveal the hepatoprotective effect of ghrelin against CP. Therefore, ghrelin might be useful in protecting the body against the adverse impacts of injuries induced by chemotherapeutic drugs.