Search

This chapter on “Cancer Traits; Present and Future” begins with a description of the process of carcinogenesis and, finally, the abnormal process leading to carcinogenesis. Cancer is a multi-step mechanism in which cells undergo biochemical and behavioral changes, causing them to proliferate in an unnecessary and untimely manner. These changes occur from modifications in mechanisms that regulate cell proliferation and longevity, relationships with neighboring cells, and the ability to escape the immune system. Modifications that contribute to cancer require genetic modifications that alter the DNA sequence. Another way to alter the program of cells is to adjust the conformation of chromatin, the matrix that bundles up DNA and controls its access through DNA reading, copying and repair machinery. These modifications are called “epigenetic. The abnormal process that leads to carcinogenesis includes early mutational events in carcinogenesis, microRNAs in human cancer and cancer stem cell hypothesis, Contact inhibition of proliferation, autophagy, necroptosis, signaling pathways, telomere deregulation, microenvironment, growth suppressors evasion, resisting cell death and sustained cell survival, enabling replicative immortality through activation of telomeres, inducing angiogenesis, ability to oppose apoptosis, and activating invasion and metastasis. Intensive research efforts during the last several decades have increased our understanding of carcinogenesis and have identified a genetic basis for the multi-step process of cancer development. Recognition and understating of the prevalent applicability of cancer cell characterization will increasingly affect the development of new means to treat human cancer.

The dried root of Dipsacus asperoides is known as Radix Dipsaci extract(RDE). It's a kidney-toning herbal medication with a lengthy track record of safe usage in the treatment of bone fractures and joint disorders. The drug rosiglitazone (RSG) causes an imbalance in bone remodelling, which results in increased apoptotic death of osteogenic cells and decreased bone production. The goal of this study was to investigate the effects of RDE on RSGinduced bone loss in diabetic rats in a systematic way. Five groups of six Wistar albino rats were studied: control (vehicle therapy), Streptozotocin (diabetes) group, RDE group, Rosiglitazone, and Rosiglitazone +RDE group. Insulin, oxidative stress, and bone turnover markers in the blood were all detected using ELISA tests. When compared to diabetic control rats, RDE therapy significantly raised insulin and osteocalcin levels. RDE may be able to prevent diabetic osteoporosis by boosting osteogenesis and lowering oxidative stress in the bone.These findings support the use of RDE as a bone loss inhibiting in diabetics. Well-designed clinical trials are likely to yield further scientific evidence on its bone-protective effects and safety. Keywords: Radix Dipsaci, Diabetic osteoporosis, Rosiglitazone.

Osteoporosis is a condition marked by a loss of bone mass and degradation of the bone microstructure, both of which lead to increased fragility and consequent fragility fractures, particularly in the elderly. Rhizoma Drynariae (DRE) is one of the most often used herbal remedies for osteoporosis therapy. Transdermal drug administration is a well- established new method for drug delivery that offers numerous benefits over conventional routes. Wistar albino rats were split into five groups of six rats each: vehicle control, diabeticgroup, DRE group, Canagliflozin (CGF), and CGF + DRE group. Each medication was given by gastric gavage once a day for 35 days. The drug canagliflozin appears to raise the risk of fractur. When compared to the control group, DRE treatment increased bone strength at the femoral diaphysis in osteoporotic fractures in rats by increasing ultimate load and stiffness. The goal of this study is to investigate the anti-osteoporosis effects of DRE in diabetic rats co-treated with CGF. Blood glucose levels and bone mineral density (BMD) were measured. According to the data, DRE produced a significant increase in bone amount. DRE may help prevent and cure diabetic osteoporosis by increasing bone mineral density, according to one study. Keywords: Rhizoma Drynariae Diabetic osteoporosis, Streptozotocin induced diabetes, Canagliflozin

The root of Pueraria labata, Puerariae radix(PR), a leguminous plant that grows wild, is one of the first and most significant basic herbs used in traditional medicine for a variety of therapeutic uses. PR is high in isoflavonoids including daidzein and genistein, which have been shown to protect against bone loss caused by oestrogen insufficiency. In an osteoporotic animal model, soybean isoflavones have been shown to reduce bone loss. CGF (canagliflozin) appears to raise the risk of fractur. In diabetic rats, the potential function of PR in reversing CGFinduced bone loss was investigated. A rat model was used to investigate the effects of Puerariae radix extract (PRE) on blood glucose, HBA1C levels, and bone mineral density. Control group (vehicle therapy), Diabetic group, `PRE group, Canagliflozin (CGF), and CGF +PRE group were all made up of six Wistar albino rats. Each medication was given by gastric gavage once a day for 35 days. PRE treatment increased bone mass substantially when compared to normal controls. This suggests that PRE might be developed as an alternative therapy for osteoporosis caused by anti-diabetic drugs. Keywords: Puerariae radix, Diabetic osteoporosis, streptozotocin, Canagliflozin.

Diabetes mellitus patients are more prone to suffer from bone fractures. Herba Epimedii has been demonstrated to be an osteoporosis reducer in the past. However, it is yet uncertain if Herba Epimedii may protect diabetic rats from bone loss when co-administered with rosiglitazone (RSG). This study examines the impact of Herba Epimedii on bone oxidative stress and turnover markers in diabetic rats co-treated with rosiglitazone (RSG). Streptozotocin (STZ) causes diabetics. Wistar albino rats were placed into five groups, each with six rats: control (vehicle therapy), Streptozotocin (diabetes) group, Herba Epimedii group, Rosiglitazone, and Rosiglitazone +Herba Epimedii. Each medication was given by gastric gavage once a day for 35 days. Insulin, oxidative stress, and bone turnover markers were measured in the blood using ELISA assays. Insulin and osteocalcin levels were significantly higher in diabetic rats administered Herba Epimedii than in diabetic control rats. Herba Epimedii may be able to prevent diabetic osteoporosis in RSG-treated diabetic rats by enhancing osteogenesis and lowering bone oxidative stress. The utility of Herba Epimedii as an osteoporosis therapy in diabetic individuals is supported by these findings. Keywords: Herba Epimedii, Diabetes, Osteoporosis, Rosiglitazone

BACKGROUND Development of new analgesics is limited by shortcomings of existing preclinical screening assays such as wide variations in response, suitability for a narrow range of analgesics, and propensity to induce tissue damage. Our aim was to determine the feasibility of a new in vivo animal assay as an analgesic screen based on nociceptive responses (licking and biting) after intraplantar (i.pl.) injection of hypertonic saline (HS) in mice. METHODS With approval from the Institutional Animal Care Committee, we conducted a randomized, investigator-blinded in vivo study in adult CD-1 mice. We first studied the concentration-response relationship, time course, and sex difference of animals' nociceptive responses to HS. Subsequently, we assessed the screening ability of the HS assay to detect a range of established analgesics belonging to different classes. Finally, we performed histopathologic studies to assess potential tissue damage. RESULTS The response produced by i.pl. HS was greater and longer in female than in male mice. The responses to HS were concentration dependent with minimal variance. Ten percent HS evoked a maximal response within the first 5 minutes. Morphine dose-dependently attenuated animals' nociceptive responses (1-10 mg/kg intraperitoneally [i.p.]). The peripherally restricted µ-opioid receptor agonist, loperamide, reduced nociceptive responses when injected locally (30-100 µg/paw, i.pl.) but not systemically (1-10 mg/kg, i.p.). Acetylsalicylic acid (300 mg/kg, i.p.), naproxen (150 mg/kg, i.p), and acetaminophen (300 mg/kg, i.p.) all decreased nociceptive responses, as did i.pl. coinjections of lidocaine (0.003%-1%) with 10% HS. Histopathologic assessment revealed no tissue damage due to HS. CONCLUSIONS The i.pl. HS assay is easily performed, rapidly detects standard analgesics, and produces minimal animal suffering without tissue damage. We propose this assay as a useful addition to the armamentarium of existing preclinical analgesic screens.

Objectives: To measure prevalence of vitamin D deficiency in Saudi Arabia, unveil the life style, nutritional habits and status, as well as identify the potential risk factors. Method: A school-based survey targeting Saudi school students and employees was conducted during the period from 2013 to 2014 using multistage cluster random sample in Central, Western and Eastern regions. The prevalence of vitamin D deficiency and difference between various population subgroups were calculated. Logistic regression analysis was used to determine the predictors of potential risk factors. Results: Prevalence of vitamin D deficiency was 49.5% in students and 44% in employees. Life style was not adequate to protect against vitamin D depletion. Unhealthy nutritional habits were widespread, some manifested in childhood while others manifested later in life. Living in the Eastern region, females, 16-19 years of age, low economic class, obese and lack of omega 3 supplements were risk factors in students. Employees living in the Eastern region, females, middle-income class, carbonated soft drink consumers, and lack of multivitamin supplements were at higher risk. Conclusion: There is a need for a health awareness program using evidence-based recommendations. Screening for early detection and correction of the condition should be proposed to be part of the national health strategy. There is need for identifying the burden of vitamin D deficiency on other diseases to control and improve the prognosis of these conditions.

The aim of this study is to investigate the antimicrobial synergistic effect against Campylobacter jejuni, a leading foodborne pathogen that causes human gastroenteritis, by cinnamon oil, encapsulated curcumin, and zinc oxide nanoparticles (ZnO NPs). We compared three approaches to study the antimicrobial interactions, including the time-killing method, the fractional inhibitory concentration index (FICI) method, and a mathematical concentration-effect model. Isobologram analysis was performed to evaluate the synergy in different combinations, and a median-effect equation was applied to identify the combinations of synergistic effects at median, bacteriostatic, and bactericidal reduction levels. The time-killing method overestimated the synergistic interaction between antimicrobials, while the FICI method failed to detect an existing synergistic phenomenon. This lack of accuracy and sensitivity was mainly due to combining antimicrobials without a deep understanding of their concentration-effect relationships. Our results showed that each antimicrobial had a unique concentration-effect curve. Specifically, encapsulated curcumin showed a sharp sigmoidal curve unlike cinnamon oil and zinc oxide nanoparticles. A mathematical model was applied to study the interaction between antimicrobials with a different shape of concentration-effect curve. We observed an additive effect of cinnamon oil/ZnO NPs and synergistic interactions of other binary combinations (cinnamon oil/encapsulated curcumin and ZnO NPs/encapsulated curcumin). The tertiary combination of cinnamon oil/ZnO NPs/encapsulated curcumin at IC25 (additive line

R-isovaline is a non-proteinogenic amino acid which produces analgesia in a range of nociceptive assays. Mediation of this effect by metabotropic receptors for γ-aminobutyric acid (GABA) and glutamate, demonstrated by previous work, may depend on the type of tissue or receptor system. The objective of this study was to assess the activity of R-isovaline acting at GABAB and group II metabotropic glutamate receptors in guinea pig ileum, which is known to exhibit well-defined responses to GABAB agonists such as baclofen. The effects of bath-applied R-isovaline and RS-baclofen were examined on electrically evoked contractions of guinea pig ileum and during GABAB antagonism by CGP52432. In separate experiments, the group II metabotropic glutamate receptor agonist, LY354740 was applied to determine the functional presence of these receptors. R-isovaline (1-100mM) decreased the amplitude of ileal muscle contractions and increased tension. RS-baclofen reduced contraction amplitude, but decreased tension. CGP52432 did not prevent the effects of R-isovaline on contraction amplitude, but antagonized effects of RS-baclofen on contraction amplitude. The group II metabotropic glutamate receptor agonist, LY354740, produced no detectable effects on evoked contractions. R-isovaline differed significantly from RS-baclofen in its actions in the guinea pig ileum, indicated in particular by the finding that CGP52432 blocked only the effects of RS-baclofen. The ileal tissue did not respond to a group II metabotropic glutamate receptor agonist, previously shown to co-mediate R-isovaline analgesia. These findings raise the possibility of a novel therapeutic target at unknown receptors for R-isovaline-like compounds in the guinea pig ileum.

Objectives: To measure prevalence of vitamin D deficiency in Saudi Arabia, unveil the life style, nutritional habits and status, as well as identify the potential risk factors. Method: A school-based survey targeting Saudi school students and employees was conducted during the period from 2013 to 2014 using multistage cluster random sample in Central, Western and Eastern regions. The prevalence of vitamin D deficiency and difference between various population subgroups were calculated. Logistic regression analysis was used to determine the predictors of potential risk factors. Results: Prevalence of vitamin D deficiency was 49.5% in students and 44% in employees. Life style was not adequate to protect against vitamin D depletion. Unhealthy nutritional habits were widespread, some manifested in childhood while others manifested later in life. Living in the Eastern region, females, 16-19 years of age, low economic class, obese and lack of omega 3 supplements were risk factors in students. Employees living in the Eastern region, females, middle-income class, carbonated soft drink consumers, and lack of multivitamin supplements were at higher risk. Conclusion: There is a need for a health awareness program using evidence-based recommendations. Screening for early detection and correction of the condition should be proposed to be part of the national health strategy. There is need for identifying the burden of vitamin D deficiency on other diseases to control and improve the prognosis of these conditions.

R-isovaline is a non-proteinogenic amino acid which produces analgesia in a range of nociceptive assays. Mediation of this effect by metabotropic receptors for γ-aminobutyric acid (GABA) and glutamate, demonstrated by previous work, may depend on the type of tissue or receptor system. The objective of this study was to assess the activity of R-isovaline acting at GABA

We previously showed that isovaline is a peripheral analgesic which acts in vivo and in brain slices as an atypical metabotropic GABA B agonist. Peripheral inhibitory group II and III metabotropic glutamate receptors (mGluRs) belong to the same family C as GABA B receptors; therefore, we hypothesized that isovaline’s analgesic effects could include their activation. We examined the effects of R-isovaline on mechanical allodynia produced by prostaglandin E 2 in the mouse paw. Subcutaneous R-isovaline produced dose-dependent antiallodynia restricted to the injected hindlimb. This antiallodynia was blocked by co-injection with a selective group II mGluR antagonist, LY341495, but not a group III mGluR antagonist (MAP-4). The antiallodynic effect of R-isovaline was potentiated by co-administration of a group II mGluR-positive allosteric modulator, LY487379. Injection of a group II mGluR agonist (LY354740) produced an antiallodynic effect which was completely reversed by group II antagonism, but was not affected by group III or GABA B (CGP35348) antagonism. Similarly, group II mGluR antagonism did not alter the antiallodynia produced by the prototypical GABA B agonist, baclofen. Hence, there was no apparent crosstalk between group II mGluRs and GABA B receptors. Previous studies have demonstrated that peripheral GABA B receptor activation by isovaline produces antiallodynia. In addition, the present results indicate that activation of peripheral group II mGluRs by R-isovaline produces antiallodynia.