Biallelic Variants in Seven Different Genes Associated with Clinically Suspected Bardet-Biedl Syndrome

Bardet-Biedl syndrome (BBS) is a rare clinically and genetically heterogeneous autosomal recessive multi-systemic disorder with 22 known genes. The primary clinical and diagnostic features include six different hallmarks, such as rod-cone dystrophy, learning difficulties, renal abnormalities, male hypogonadism, post-axial polydactyly, and obesity. Here, we report nine consanguineous families and a non-consanguineous family with several affected individuals presenting typical clinical features of BBS. In the present study, 10 BBS Pakistani families were subjected to whole exome sequencing (WES), which revealed novel/recurrent gene variants, including a homozygous nonsense mutation (c.94C>T; p.Gln32Ter) in the IFT27 (NM_006860.5) gene in family A, a homozygous nonsense mutation (c.160A>T; p.Lys54Ter) in the BBIP1 (NM_001195306.1) gene in family B, a homozygous nonsense variant (c.720C>A; p.Cys240Ter) in the WDPCP (NM_015910.7) in family C, a homozygous nonsense variant (c.505A>T; p.Lys169Ter) in the LZTFL1 (NM_020347.4) in family D, pathogenic homozygous 1 bp deletion (c.775delA; p.Thr259Leufs*21) in the MKKS/BBS5 (NM_170784.3) gene in family E, a pathogenic homozygous missense variant (c.1339G>A; p.Ala447Thr) in BBS1 (NM_024649.4) in families F and G, a pathogenic homozygous donor splice site variant (c.951+1G>A; p?) in BBS1 (NM_024649.4) in family H, a pathogenic bi-allelic nonsense variant in MKKS (NM_170784.3) (c.119C>G; p.Ser40*) in family I, and homozygous pathogenic frameshift variants (c.196delA; p.Arg66Glufs*12) in BBS5 (NM_152384.3) in family J. Our findings extend the mutation and phenotypic spectrum of four different types of ciliopathies causing BBS and also support the importance of these genes in the development of multi-systemic human genetic disorders

Case report: A novel de novo loss of function variant in the DNA-binding domain of TBX2 causes severe osteochondrodysplasia

Background: T-box family members are transcription factors characterized by highly conserved residues corresponding to the DNA-binding domain known as the T-box. TBX2 has been implicated in several developmental processes, such as coordinating cell fate, patterning, and morphogenesis of a wide range of tissues and organs, including lungs, limbs, heart, kidneys, craniofacial structures, and mammary glands.Methods: In the present study, we have clinically and genetically characterized a proband showing a severe form of chondrodysplasia with developmental delay. Whole-exome sequencing (WES), Sanger sequencing, and 3D protein modeling were performed in the present investigation.Results: Whole-exome sequencing revealed a novel nonsense variant (c.529A>T; p.Lys177*; NM_005994.4) in TBX2. 3D-TBX2 protein modeling revealed a substantial reduction of the mutated protein, which might lead to a loss of function (LOF) or nonsense-mediated decay (NMD).Conclusion: This study has not only expanded the mutation spectrum in the gene TBX2 but also facilitated the diagnosis and genetic counseling of related features in affected families

Antihyperlipidemic effects of Citrus sinensis, Citrus paradisi, and their combinations

Objective: Hyperlipidemia, extensively contributes in the progression of coronary heart diseases and atherosclerosis, but may be managed through alterations in the nutritional pattern. Several studies show that diet rich in polyphenols and antioxidants have antiatherogenic effects. Citrus sinensis and Citrus paradisi are widely known for health benefits and have found to produce antioxidant, anti-inflammatory, and hypolipidemic effects, hence current research was planned to determine the hypolipidemic effects of C. sinensis and C. paradisi in rats receiving diet rich in cholesterol. Materials and Methods: All rats were divided into 11 groups each comprising 10 animals: Normal control group and hyperlipidemic control. C. sinensis treated three groups, C. paradisi treated three groups, C. sinensis and C. paradisi combination treated two groups, and group treated atorvastatin. All rats in the respective groups were treated orally with sterile water, juices, and standard drug for 8 weeks and lipid profile was estimated at the end of dosing. Results: Cholesterol, triglycerides (TGs), and low-density lipoprotein (LDL) were decreased at all the three doses of C. sinensis and C. paradisi but rise in high-density lipoprotein (HDL) was only significant at 8 ml/kg, and 0.3 ml/kg, respectively. Animals received the combination doses of C. sinensis and C. paradisi also showed a highly significant fall in cholesterol, LDL, and TGs, however HDL level was significantly elevated by SPJ-2 combination. Conclusion: Results suggest that C. sinensis and C. paradisi possess antihyperlipidemic activity due to phytochemicals and other essential nutrients, hence may serve as cardioprotective by preventing thrombosis

Nootropic Effects of C. melo and C. lanatus seed extracts

Dementia and related conditions disturb the ability to perform routine life activities prohibiting a person from making appropriate decisions. Seeds of Cucumis melo and Citrullus lanatus have been investigated extensively for various pharmacological properties; hence, considering the presence of bioactive compounds, it was assumed that these seed extracts may support the functioning of the central nervous system. Thus, the present study was designed to investigate the short-term and long-term memory-enhancing effects of C. melo and C. lanatus seed extracts in mice by the Morris water maze (spatial learning and memory), stationary rod test, and passive avoidance tests (fear-motivated tests). Ethanol extract of both seeds were prepared by standard procedure and given to animals in the doses of 50 mg/kg, 100 mg/kg, and 200 mg/kg. The results were compared to standard drugs diazepam and imipramine given in the doses of 3 mg/kg and 30 mg/kg, respectively. Extracts of both the seeds were found to possess significant memory and cognition-enhancing effects in mice when tested by passive avoidance, stationary rod, and water maze tests. Results demonstrate memory and cognition-enhancing effects of these extracts which may be due to the presence of bioactive compounds in these seeds

Cucurbita maxima Seeds Reduce Anxiety and Depression and Improve Memory

The current study was planned to assess the neuropharmacological benefits of the Cucurbita maxima seed. These seeds have been conventionally used for the nutritional as well as amelioration of various diseases. However, there was a need to provide a pharmacological basis for such use. Four central nervous system-related functions, that is, anxiety, depression, memory, and motor coordination, were evaluated, and the levels of brain biogenic amines were also assessed. Anxiety was evaluated through selected experimental models, such as light and dark apparatus, elevated plus maze, head dip, and open field test. The head dip test was mainly used to assess exploratory behavior. Depression was assessed by two animal models, that is, the forced swim test and tail suspension test. Memory and learning ability were assessed by the passive avoidance test, stationary rod apparatus, and Morris’s water maze test. Motor skilled learning was assessed by stationary rod and rotarod apparatus. Reversed phase high-pressure liquid chromatography was used to determine biogenic amine levels. Results reveal that C. maxima exhibited anxiolytic and antidepressant effects with memory improvement. There was a reduction in the weight of the animal following chronic administration. Furthermore, no remarkable effects were observed on motor coordination. Norepinephrine was found elevated, which may be linked to its antidepressant effects. These biological effects of C. maxima may be due to the presence of secondary metabolites, such as cucurbitacin, beta-sitosterol, polyphenolic compounds, citrulline, kaempferol, arginine, β-carotene, quercetin, and other antioxidants. The outcomes of the present study authenticate that the chronic use of C. maxima seeds reduces the intensity of neurological problems like anxiety and depression

Efficacy of Metronidazole in Combination with Amoxicillin and Doxycycline in Adult Periodontitis

Objective:Periodontal diseases are amongst most prevalent diseases in the world. They are caused by poor oral hygiene, accumulation of dental plaque and virulent putative pathogens on the teeth and gums Systemic antibiotics are used as adjuncts for the treatment of this infective disease. The objective of this study was to compare the efficacy of two antibiotic drug combinations i.e., Metronidazole with Amoxicillin and Metronidazole with Doxycycline in patients with adult periodontitis.Method:50 patients were divided in two groups. They were given fixed doses for 7 days to patients with Adult Periodontitis. Readings were taken before treatment and two weeks prior to the treatment. The result was evaluated on the basis of periodontal Pocket depth, Bleeding Index and Mobility Index. The readings were taken using Periodontal Probe, dental Mirror and dental Explorer.Result: There was significant reduction (

Comparison of Hepatic Parameters Following Administration of Antihypertensive, Hypolipidemic and Hypoglycemic Drugs

The risk of additive effects of drugs has remained a continuous concern while prescribing more than one drug to a patient, and it becomes more of a problem when the patient suffers from various diseases simultaneously. In this reasearch the drug taking pattern of elderly patients was kept in mind and the antihyperlipidemic, oral hopoglycemic and antihypertensive commonly prescribed in combinations or as individual agents were given to the rabbits for period of two months and their effects on liver function tests were noted. As compared to control rabbits, Acarbose and Glibenclamide decreased Direct bilirubin (DBR), where as Lisinopril and Amlodipine increased it (P<0.05). Atorvastatin and Amlodipine increased Total bilirubin (TBR) (P<0.05). Acarbose and Metformin increased, where as Atorvastatin decreased Glutamic-Pyruvic Transaminase (GPT) (P<0.05). Metformin and Lisinopril decreased (P<0.05) where as Losartan increased ALP(alkaline phosphatase) (P<0.005). Losartan and Atorvastatin increased Gamma Glutamyl Transferase γ-GT (P<0.005)

Does atorvastatin work more effectively than biguanides in reducing cardiovascular risk factors?

Increased risk of coronary artery disease in diabetic persons is associated with increased level of lipoproteins. Usually, such risks are reverted with glycemic control by antidiabetic medicines in Type I diabetes millitus. However, in Type II diabetes mellitus lipid values can be improved using antidiabetics but still the risk of coronary artery disease remains. The initial approach for reducing lipid contents in diabetic patients should include glycemic control, diet, weight loss, and exercise. But if it fails then lipid-lowering agents like fibrate and HMG CoA reductase (3-hydroxy-3-methyl-glutaryl-CoA reductase) inhibitors should work effectively. In the present study results of atorvastatin compared with biguanides proved atorvastatin as a more effective lipid-lowering agent along with antidiabetic activity so it can effectively help in reducing the risk of cardiovascular disease (CVD)

Efficacy of Metronidazole in Combination with Amoxicillin and Doxycycline in Adult Periodontitis

Objective:Periodontal diseases are amongst most prevalent diseases in the world. They are caused by poor oral hygiene, accumulation of dental plaque and virulent putative pathogens on the teeth and gums Systemic antibiotics are used as adjuncts for the treatment of this infective disease. The objective of this study was to compare the efficacy of two antibiotic drug combinations i.e., Metronidazole with Amoxicillin and Metronidazole with Doxycycline in patients with adult periodontitis.Method:50 patients were divided in two groups. They were given fixed doses for 7 days to patients with Adult Periodontitis. Readings were taken before treatment and two weeks prior to the treatment. The result was evaluated on the basis of periodontal Pocket depth, Bleeding Index and Mobility Index. The readings were taken using Periodontal Probe, dental Mirror and dental Explorer.Result: There was significant reduction (