Assessment of the association of CYP1A1 gene polymorphisms with the susceptibility of cervical cancer: A case-control study and meta-analysis.

Background: Cervical cancer (CC) is the second most common type of female malignancy in Bangladesh. Polymorphisms in the CYP1A1 gene have been reported to be associated with CC in different populations. This case-control study with meta-analysis was undertaken to assess the relation of CYP1A1 rs4646903 and rs1048943 polymorphisms with the susceptibility of CC. Methods: A total of 185 CC patients and 220 controls were recruited, and the PCR-RFLP (Polymerase chain reaction-restriction fragment length polymorphism) technique was applied for genotyping. Again, 42 eligible studies (24 with rs4646903 and 18 with rs1048943) were included for meta-analysis, and RevMan 5.3 and the MetaGenyo web-based tool were used. Results: The rs4646903 polymorphism was significantly linked with CC in all association models, namely, additive 1, additive 2, dominant, recessive, overdominant, and allele models (OR = 2.41, 4.75, 2.67, 3.61, 2.13, and 2.44 with corresponding 95% CI = 1.55-3.76, 1.81-12.45, 1.75-4.07, 1.39-9.35, 1.38-3.30, and 1.71-3.48, respectively). On the contrary, rs1048943 showed no association (p > 0.05) with CC. Haplotype analysis revealed AT and AC haplotypes significantly decreased (OR = 0.45) and increased (OR = 4.86) CC risk, respectively, and SNPs are in strong linkage disequilibrium (D' = 0.912, r2 = 0.448). Again, rs4646903 carriers with a contraception history and >5 years of taking contraceptives showed an enhanced risk of CC (OR = 2.39, OR = 3.05). Besides, rs1048943 carriers aged >40 years (OR = 0.44), conceived first child aged ≤18 years (OR = 3.45), and history of contraceptives (OR = 2.18) were significantly linked with CC. Our meta-analysis found that for CYP1A1 rs4646903 codominant 1 (COD 1), codominant 2 (COD 2), codominant 3 (COD 3), dominant model (DM), recessive model (RM), and allele model (AM) in Caucasians and overdominant model (OD) in the overall population are associated with an elevated risk of CC, whereas rs1048943 is also associated with CC in overall, Caucasians and Asians in some genetic models. Conclusion: Our case-control study and meta-analysis summarize that CYP1A1 rs4646903 and rs1048943 polymorphisms may be correlated with cervical cancer.

Acute and subchronic toxicity profile of methanol extract of leaves of Fimbristylis miliacea (L.) Vahl.

Ethnopharmacological relevance: Fimbristylis miliacea (L.) Vahl (Cyperaceae) is a grass like herb habitually breeds as weed in paddy fields and mostly disseminated in tropical or sub-tropical countries of south and south-east Asia, northern Australia, and west Africa. The plant has been traditionally used to treat fever as a form of poultice. However, no scientific study regarding its toxicity profile has been testified. Aim of the study: The study has been carried out to determine the potential toxicity of the methanol extract from leaves of the Fimbristylis miliacea, employing the technique of acute and subchronic oral administration in mice. Materials and methods: In the acute toxicity study according to OECD guideline 425, oral administration of FM methanol extract at single doses of 2000 and 5000 mg/kg in both sexes of Swiss albino mice was performed. Toxic symptoms, abnormal behavior, changes in body weight, and mortality were observed for 14 consecutive days. In subchronic toxicity study according to OECD guideline 407, plant extract was administered orally at doses of 100, 500, 1000, and 2000 mg/kg daily for 28 days. The general toxic symptoms, abnormal behavior, changes in body weight were observed daily. Biochemical analysis of serum, and histopathological examination of liver were performed at the end of the study. Results: No mortality, abnormal behavior and urination, changes in sleep, food intake, adverse effect, and non-linearity in body weight have been recorded during acute toxicity study at the doses of 2000 and 5000 mg/kg. Also, in subchronic toxicity study, FM extract produced no mortality or any kind of adverse effects in regards of general behavior, body weight, urination, sleeping routine, and food intake. In case of analysis of thirteen different biochemical parameters, concentrations of aspartate transaminase (AST) and glucose were altered significantly in male and female mice in both acute and subchronic study. Total cholesterol and triglycerides at 5000 mg/kg.bw were changed in male mice in acute toxicity study. On the other hand, female mice had altered triglycerides in subchronic test. All other critical parameters were found unaffected. In subchronic test, histopathological examination of liver demonstrated cellular necrosis at 2000 mg/kg.bw in both male and female mice while minor necrosis was observed at 1000 mg/kg.bw. Thus, the no observed adverse effect level (NOAEL) can be assumed around 1000 mg/kg.bw. Conclusion: The present study suggests that treatment with FM extract does not reveal significant toxicity.

Propagation of age-related diseases due to the changes of lipid peroxide and antioxidant levels in elderly people: A narrative review.

Background and Aims: Lipid peroxidation end products are the major culprit for inducing chronic diseases in elderly people. Along with the elevated level of lipid peroxide biomarkers, there is a significant disruption of antioxidants balance, which combinedly propagate the diseases of elderly people. The aim of the present review is to bridge the connection of changes in lipid peroxides biomarkers and antioxidants level with age-associated diseases in elderly people. Methods: This narrative review was performed following a comprehensive search for suitable articles in multiple online databases, including PubMed, Google Scholar, EMBASE, Web of Science, Cochrane Library, and ScienceDirect using selected search terms. The most appropriate literature was included based on the selection criteria. Results: From the review, it is found that many age-related diseases propagated with an increased level of the end products of lipid peroxide and reduced levels of antioxidants in elderly people. When the end products of lipid peroxidation increase in the body, it creates oxidative stress, which ultimately leads to many complicated diseases, including cancers, cardiovascular and neurogenic diseases, and many other chronic inflammatory diseases. The oxidative stress induced by peroxidation can be assessed by different lipid peroxide end products such as malondialdehyde, oxidized low-density lipoprotein, isoprostanes, neuroprostanes, lipoperoxides, oxysterols (7-ketocholesterol, 7ß-hydroxycholesterol), and many more. Conclusions: This study definitively answers the correlation between the changes in lipid peroxides and antioxidants level and age-related diseases. Our narrative article recommends future investigations for elucidating the mechanisms rigorously to establish a compact correlation.

LED Illumination for High-Quality High-Yield Crop Growth in Protected Cropping Environments.

Vegetables and herbs play a central role in the human diet due to their low fat and calory content and essential antioxidant, phytochemicals, and fiber. It is well known that the manipulation of light wavelengths illuminating the crops can enhance their growth rate and nutrient contents. To date, it has not been easy to generalize the effects of LED illumination because of the differences in the plant species investigated, the measured traits, the way wavelengths have been manipulated, and the plants' growing environments. In order to address this gap, we undertook a quantitative review of LED manipulation in relation to plant traits, focusing on vegetables and herbs. Here, we use standardized measurements of biomass, antioxidant, and other quantitative characteristics together with the whole range of the photosynthetic photon flux density (PPFD). Overall, our review revealed support for the claims that the red and blue LED illumination is more reliable and efficient than full spectrum illumination and increases the plant's biomass and nutritional value by enhancing the photosynthetic activity, antioxidant properties, phenolic, and flavonoids contents. Although LED illumination provides an efficient way to improve yield and modify plant properties, this study also highlights the broad range of responses among species, varieties traits, and the age of plant material.

Antidiabetic and hepatoprotective potential of whole plant extract and isolated compounds of Aeginetia indica.

BACKGROUND: Aeginetia indica, a perennial herb from the Orobanchaceae family, generally grows as a root parasite and is widely distributed in the forests of South and South-Asian countries. The plant has valuable uses in herbal medicine against various diseases, such as diabetes, liver diseases, and arthritis. AIM OF THE STUDY: The present study was designed to investigate the antidiabetic and hepatoprotective effects of the methanol extract of the whole plant of A. indica in a mouse model followed by the isolation of bioactive compounds and their in-silico studies. METHODS: The hepatoprotective effects were evaluated in a paracetamol-induced hepatotoxicity mouse model. The antidiabetic effects were examined by an oral glucose tolerance test and in an alloxan-induced diabetes mouse model. RESULTS: The plant extract, at a dose of 400 mg/kg, caused a significant reduction (p < 0.001) in liver enzyme concentrations, including alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase, similar to the effects of standard drug silymarin. The plant extract, at 400 mg/kg, also significantly reduced (p < 0.001) the fasting blood glucose concentration by 27.33 % after 3 h, compared with a reduction of 45.31 % in response to glibenclamide. In the alloxan-induced diabetes model mice, significant reductions (p < 0.05) in elevated glucose concentrations were observed on days 10 and 20 in mice treated with plant extract and glibenclamide. Chromatographic analyses and nuclear magnetic resonance (NMR) studies identified the presence of ß-sitosterol, stigmasterol, and oleic acid in the extract. The possible mechanism underlying the antidiabetic effects was revealed by molecular docking analyses examining the binding of ß-sitosterol and stigmasterol with sirtuin 4, an NAD-dependent deacylase enzyme that downregulates leucine-induced and glutamate dehydrogenase-induced insulin secretion. The binding affinities between sirtuin 4 and ß-sitosterol, stigmasterol, and NAD were found to be -8.6 kcal/mol, -7.2 kcal/mol and -9.5 kcal/mol, respectively, indicating the probable competition between NAD and the isolated components for sirtuin 4. CONCLUSION: The present study revealed that A. indica exerted protective effects against alloxan-induced diabetes and paracetamol-induced hepatotoxicity in mice, which supports the findings regarding the use of A. indica during traditional medical practice.

Antipyretic and anti-nociceptive effects of methanol extract of leaves of Fimbristylis miliacea in mice model.

ETHNOPHARMACOLOGICAL RELEVANCE: Fimbristylis miliacea (L.) Vahl (Cyperaceae) is a grass like herb usually grows as a weed in rice fields and is mainly distributed in tropical or sub-tropical countries of south and south-east Asia, central America, northern Australia and west Africa. The plant has been traditionally used to treat fever as a form of poultice. AIM OF THE STUDY: The present study aimed to investigate antipyretic and anti-nociceptive effects of methanol extract of leaves of Fimbristylis miliacea in mice model. MATERIALS AND METHODS: Antipyretic effect of Fimbristylis miliacea was examined using Baker's yeast induced hyperthermia test. Anti-nociceptive effect was investigated using acetic acid induced writhing test, formalin induced hind paw licking test and hot plate test. RESULTS: The extract at concentration of 400 mg/kg produced significant reduction in body temperature after 0.5 h of administration (4.12 °F, p ≤ 0.001) and continued to decrease (after 4 h, 5.92 °F, p ≤ 0.001). Extracts at 100 mg/kg and 200 mg/kg decreased the temperature by about 2.77 °F (from 99.47 °F to 96.7 °F) and 5.58 °F (98.2 °F-92.62 °F) respectively after 4 h whereas paracetamol dropped by about 7.2 °F (p ≤ 0.001). The extract showed significant decrease in number of writhes at all concentrations. Highest effect was found at 200 mg/kg having 35.7 writhes (p ≤ 0.001), much lower than control (89.2); standard drug diclofenac showed 23.2 writhes. Percent inhibition of writhing were 54.26 and 73.99 for 200 mg/kg and diclofenac respectively. The result of hind paw licking test also corroborated writhing test. Significant reduction in percent inhibition of licking was observed mainly in late phase. Percent inhibition of licking were 93.77 and 51.55 for 400 mg/kg extract and diclofenac respectively. In hot plate test, extract at 400 mg/kg showed significant increase in latency from 10.77 s to 13.59 s (p ≤ 0.05). Extract at this dose after 2 h demonstrated greater percent maximal effect (43.26%) compared to ketorolac (40.19%). CONCLUSION: The experiment confirmed the traditional use of F. miliacea in the treatment of fever with possible anti-nociceptive effects.

Sequence-selective binding of C8-conjugated pyrrolobenzodiazepines (PBDs) to DNA.

DNA footprinting and melting experiments have been used to examine the sequence-specific binding of C8-conjugates of pyrrolobenzodiazepines (PBDs) and benzofused rings including benzothiophene and benzofuran, which are attached using pyrrole- or imidazole-containing linkers. The conjugates modulate the covalent attachment points of the PBDs, so that they bind best to guanines flanked by A/T-rich sequences on either the 5'- or 3'-side. The linker affects the binding, and pyrrole produces larger changes than imidazole. Melting studies with 14-mer oligonucleotide duplexes confirm covalent attachment of the conjugates, which show a different selectivity to anthramycin and reveal that more than one ligand molecule can bind to each duplex.

DNA sequence-selective C8-linked pyrrolobenzodiazepine-heterocyclic polyamide conjugates show anti-tubercular-specific activities.

New chemotherapeutic agents with novel mechanisms of action are in urgent need to combat the tuberculosis pandemic. A library of 12 C8-linked pyrrolo[2,1-c][1,4]benzodiazepine (PBD)-heterocyclic polyamide conjugates (1-12) was evaluated for anti-tubercular activity and DNA sequence selectivity. The PBD conjugates were screened against slow-growing Mycobacterium bovis Bacillus Calmette-Guérin and M. tuberculosis H37Rv, and fast-growing Escherichia coli, Pseudomonas putida and Rhodococcus sp. RHA1 bacteria. DNase I footprinting and DNA thermal denaturation experiments were used to determine the molecules' DNA recognition properties. The PBD conjugates were highly selective for the mycobacterial strains and exhibited significant growth inhibitory activity against the pathogenic M. tuberculosis H37Rv, with compound 4 showing MIC values (MIC=0.08 mg l-1) similar to those of rifampin and isoniazid. DNase I footprinting results showed that the PBD conjugates with three heterocyclic moieties had enhanced sequence selectivity and produced larger footprints, with distinct cleavage patterns compared with the two-heterocyclic chain PBD conjugates. DNA melting experiments indicated a covalent binding of the PBD conjugates to two AT-rich DNA-duplexes containing either a central GGATCC or GTATAC sequence, and showed that the polyamide chains affect the interactions of the molecules with DNA. The PBD-C8 conjugates tested in this study have a remarkable anti-mycobacterial activity and can be further developed as DNA-targeted anti-tubercular drugs.

Current distribution and status of Himalayan ibex in upper Neelum Valley, District Neelum Azad Jammu and Kashmir, Pakistan.

Nine months field survey was conducted from July 2004 to August 2005 to take the data on the distribution and population status of Himalayan ibex (Capra ibex sibirica) in the upper Neelum valley of Azad Kashmir. Survey was carried out using direct (senses) as well as indirect (sampling) methods. 122 animals of different categories were recorded in the study area. Total average population was composed of 31.79% male, 32.79% female, 25.41% young and 9.84% yearling animals. Various threats to the population of ibex in the area were also studied.