Biotechnological approaches for the production of camptothecin.

Camptothecin (CPT), an indole alkaloid popular for its anticancer property, is considered the third most promising drug after taxol and famous alkaloids from Vinca for the treatment of cancer in humans. Camptothecin was first identified in Camptotheca acuminata followed by several other plant species and endophytic fungi. Increased harvesting driven by rising global demand is depleting the availability of elite plant genotypes, such as Camptotheca acuminata and Nothapodytes nimmoniana, crucial for producing alkaloids used in treating diseases like cancer. Conservation of these genotypes for the future is imperative. Therefore, research on different plant tissue culture techniques such as cell suspension culture, hairy roots, adventitious root culture, elicitation strategies, and endophytic fungi has been adopted for the production of CPT to meet the increasing demand without affecting the source plant's existence. Currently, another strategy to increase camptothecin yield by genetic manipulation is underway. The present review discusses the plants and endophytes that are employed for camptothecin production and throws light on the plant tissue culture techniques for the regeneration of plants, callus culture, and selection of cell lines for the highest camptothecin production. The review further explains the simple, accurate, and cost-effective extraction and quantification methods. There is enormous potential for the sustainable production of CPT which could be met by culturing of suitable endophytes or plant cell or organ culture in a bioreactor scale production. Also, different gene editing tools provide opportunities for engineering the biosynthetic pathway of CPT, and the overall CPT production can be improved . KEY POINTS: • Camptothecin is a naturally occurring alkaloid with potent anticancer properties, primarily known for its ability to inhibit DNA topoisomerase I. • Plants and endophytes offer a potential approach for camptothecin production. • Biotechnology approaches like plant tissue culture techniques enhanced camptothecin production.

Status of vector protection measures and awareness regarding vector borne diseases in families residing in a "Nirmal Gram Puraskar" village in India.

BACKGROUND OBJECTIVES: Mosquito-bome diseases are increasing problems in various parts of the world, causing high mortality and morbidity for humans. This study was done to assess the vector protection measures taken by rural below poverty line (BPL) families, and to assess the awareness about vector-borne diseases along with Total Sanitation Campaign (TSC) in rural BPL families. METHODS: A cross-sectional study was conducted in a rural area which won "Nirmal Gram Puraskar" Award i.e., "clean village" among 96 below BPL families for a period of three months. These families (every 5 th ) were selected by systematic random sampling until we reached a sample size. Basic socio-demographic details, status of vector protection measures, solid waste management, vector-borne diseases and total sanitation campaign details were collected from the study participants. Pretested, semi-structured questionnaire was applied to the head of the families which included sanitation status at home by house-to-house visit. Data collected was analysed using SPSS version 20 and presented as frequency, percentages, mean and standard deviation. RESULTS: Among 96 families studied (454 adults and children), 84 (87.5%) were males and 12 (12.5%) were females. Among these, 291 (64.1%) were using one or the other mosquito protection measures, 52 (54.2%) were using bednets and 23 (23.9%) used coils. 12 families (12.5%) were not using any mosquito protection measures. In our study, 66 (68.8%) families had individual household latrine (IHHL) and 50 (52.1%) had open drainage. Even though 314 participants had an access to individual household latrine, 20 (6.36%) had practice of open air defecation compared to 127 (90.7%) who practiced open air defecation without an access to individual household latrine. When asked about the awareness regarding vector-borne diseases, 56 (58.3%) were aware about chikungunya, 47 (48.9%) about dengue, 46 (47.9%) about malaria, 14 (14.6%) and only 5 (5.2%) families were aware about Japanese encephalitis. In this study, 37 (38.5%) were aware about the total sanitation campaign and 40 (41.6%) about the government support for sanitation. INTERPRETATION CONCLUSION: While there is a general awareness of vector-borne diseases, the implementation of vector protection measures is not uniform across the village. There is a need for targeted interventions to improve the effectiveness of vector protection measures and increase awareness among the community.

Diagnostic yield and technical performance of the novel motorized spiral enteroscopy compared with single-balloon enteroscopy in suspected Crohn's disease: a prospective study (with video).

BACKGROUND AND AIMS: Both single-balloon enteroscopy (SBE) and the novel motorized spiral enteroscopy (NMSE) are effective techniques for device-assisted enteroscopy (DAE). To date, no study has prospectively compared both modalities in suspected Crohn's disease (CD). METHODS: Patients with suspected CD undergoing either SBE or NMSE between March 2021 and December 2021 in a high-volume tertiary center were prospectively compared for technical success (ability to reach the lesion), diagnostic yield, depth of maximal insertion (DMI), procedure time, and total enteroscopy rates. RESULTS: One hundred seventy-seven patients (37.2% female; aged 7-75 years) with suspected CD underwent 201 DAEs. Technical success was 83% (SBE 81.5% vs NMSE 87.3%, P = .61) and impacted subsequent management in 92% (SBE 88.5% vs NMSE 97.8%, P = .2). Technical success with antegrade NMSE was significantly higher (81.4%) than antegrade SBE (33.3%, P = .007) for lesions in the proximal ileum and beyond. There was no significant difference in the diagnostic yield (SBE 80.8% vs NMSE 83.6%, P = .65). Median procedure time was significantly lower in both antegrade (NMSE, 40 minutes [range, 10-75]; SBE, 60 minutes [range, 20-180]; P < .0001) and retrograde (NMSE, 25 minutes [range, 20-60]; SBE, 60 minutes [range, 20-180]; P < .0001) NMSE. Median DMI was higher with antegrade NMSE (NMSE, 400 cm [range, 70-600]; SBE, 180 cm [range, 60-430]; P < .0001). The total enteroscopy rate was higher with NMSE (37% vs .7% with SBE, P < .0001). All adverse events were mild. CONCLUSIONS: Both NMSE and SBE are safe and effective for small-bowel evaluation in suspected CD. NMSE is superior to SBE with regard to deeper small-bowel evaluation with complete small-bowel coverage and shorter procedure time.

Platform-agnostic electrochemical sensing app and companion potentiostat.

Electrochemical sensing is ubiquitous in a number of fields ranging from biosensing, to environmental monitoring through to food safety and battery or corrosion characterisation. Whereas conventional potentiostats are ideal to develop assays in laboratory settings, they are in general, not well-suited for field work due to their size and power requirements. To address this need, a number of portable battery-operated potentiostats have been proposed over the years. However, most open source solutions do not take full advantage of integrated circuit (IC) potentiostats, a rapidly evolving field. This is partly due to the constraining requirements inherent to the development of dedicated interfaces, such as apps, to address and control a set of common electrochemical sensing parameters. Here we propose the PocketEC, a universal app that has all the functionalities to interface with potentiostat ICs through a user defined property file. The versatility of PocketEC, developed with an assay developer mindset, was demonstrated by interfacing it, via Bluetooth, to the ADuCM355 evaluation board, the open-source DStat potentiostat and the Voyager board, a custom-built, small footprint potentiostat based around the LMP91000 chip. The Voyager board is presented here for the first time. Data obtained using a standard redox probe, Ferrocene Carboxylic Acid (FCA) and a silver ion assay using anodic stripping multi-step amperometry were in good agreement with analogous measurements using a bench top potentiostat. Combined with its Voyager board companion, the PocketEC app can be used directly for a number of wearable or portable electrochemical sensing applications. Importantly, the versatility of the app makes it a candidate of choice for the development of future portable potentiostats. Finally, the app is available to download on the Google Play store and the source codes and design files for the PocketEC app and the Voyager board are shared via Creative Commons license (CC BY-NC 3.0) to promote the development of novel portable or wearable applications based on electrochemical sensing.

Potential effects of heavy metal pollution from a cement factory near Saudi Arabia's largest green turtle rookery.

Sand samples were collected from four beaches near a cement factory in Ras Baridi, north of Yanbu, which hosts the largest green turtle rookery in Saudi Arabia. Heavy metal concentrations (Cd, Pb, Fe, Cr, Ni, Se, Sb, As, and Cu) were measured at three different depths. For most elements, there were no significant differences in concentrations among depths; however, significant differences were found among the nesting beaches in Ras Baridi, which were likely influenced by the wind direction from the factory. Fe, Cr, Cu, and Ni had elevated contamination factor values, suggesting that the nesting beaches downwind and adjacent to the cement factory contained moderately contaminated sand. Given the possibility of heavy metals being absorbed through eggshells, there is a potential risk of heavy metal contamination in clutches laid in Ras Baridi. The rising threat to the local ecology in Saudi Arabia due to recent coastal developments for tourism projects highlights the importance of monitoring heavy metal concentrations over time.

Entinostat, a selective HDAC1/2 inhibitor, potentiates the effects of olaparib in homologous recombination proficient ovarian cancer.

OBJECTIVE: Poly ADP ribose polymerase inhibitors (PARPi) are most effective in BRCA1/2 mutated ovarian tumors. Better treatments are needed for homologous recombination HR-proficient cancer, including CCNE1 amplified subtypes. We have shown that histone deacetylase inhibitors (HDACi) sensitize HR-proficient ovarian cancer to PARPi. In this study, we provide complementary preclinical data for an investigator-initiated phase 1/2 clinical trial of the combination of olaparib and entinostat in recurrent, HR-proficient ovarian cancer. METHODS: We assessed the in vitro effects of the combination of olaparib and entinostat in SKOV-3, OVCAR-3 and primary cells derived from CCNE1 amplified high grade serous ovarian cancer (HGSOC) patients. We then tested the combination in a SKOV-3 xenograft model and in a patient-derived xenograft (PDX) model. RESULTS: Entinostat potentiates the effect of olaparib in reducing cell viability and clonogenicity of HR-proficient ovarian cancer cells. The combination reduces peritoneal metastases in a SKOV-3 xenograft model and prolongs survival in a CCNE1 amplified HR-proficient PDX model. Entinostat also enhances olaparib-induced DNA damage. Further, entinostat decreases BRCA1, a key HR repair protein, associated with decreased Ki-67, a proliferation marker, and increased cleaved PARP, a marker of apoptosis. Finally, entinostat perturbs replication fork progression, which increases genome instability. CONCLUSION: Entinostat inhibits HR repair by reducing BRCA1 expression and stalling replication fork progression, leading to irreparable DNA damage and ultimate cell death. This work provides preclinical support for the clinical trial of the combination of olaparib and entinostat in HR-proficient ovarian cancer and suggests potential benefit even for CCNE1 amplified subtypes.

Role of Superficial Cervical Plexus Nerve Block as an Adjuvant to Local Anesthesia in the Maxillofacial Surgical Practice.

PURPOSE: Infiltration techniques are used as an adjuvant to regional anesthesia. In this study, we evaluated the efficacy of the superficial cervical plexus nerve block, as an alternative to local infiltration techniques; in the management of mandibular fractures and peri-mandibular space infections. METHODS: A prospective randomized controlled trial was conducted on 24 patients having either mandibular fractures or peri-mandibular space infections; and were scheduled for surgery under regional anesthesia (eg, inferior alveolar nerve block, long buccal nerve block). The control group involved delivering a combination of regional anesthesia along with local infiltration. The experimental group received regional anesthesia with a superficial cervical plexus nerve block. The following parameters were studied: pain, onset and duration of anesthesia, time interval until first analgesic request, pulse rate and blood pressure [at different time intervals]. RESULTS: Intergroup comparison was done using unpaired t-test. Intragroup comparison was done using repeated measures ANOVA (for >2 observations), followed by a post hoc test. The superficial cervical plexus nerve block group showed highly statistically significant (P < .01) improvement in terms of intra-operative pain at 30 minutes, duration of anesthesia, intraoperative anesthetic requirement, time interval until first analgesic request and intraoperative diastolic blood pressure at 10 minutes. CONCLUSION: It can be concluded that the combination of a regional anesthesia technique with a superficial cervical plexus nerve block is an alternative and safe technique for patients undergoing surgery for mandible fractures and perimandibular space infections, with clear advantages over local infiltration.

Identification of quinoline-chalcones and heterocyclic chalcone-appended quinolines as broad-spectrum pharmacological agents.

Quinoline derivatives have been reported to possess enticing pharmacological properties. In particular, quinoline-chalcones are identified as promising scaffolds for drug discovery. For a long, the quinoline analogs have been in clinical use for various medical conditions such as cancer inhibitory activity, antibacterial and antifungal, anti-plasmodial, DNA damage inhibitory activity, etc. The number of causalities recorded because of the above-mentioned clinical states is significantly large. Though drug design and discovery is a continuous process all over the world, issues like drug-resistance, low metabolic stability, and long-range side effects are potential hindrances for the continuous use of present pharmacological drugs. In this review work, we focused on the recent drug discovery based on quinoline-chalcones. The work emphasizes the potency of a wide range of quinoline chalcone analogs towards the inhibition of infections caused by the various pathogenic microbes such as bacteria, fungi, plasmodium. Alongside, the quinoline chalcones possessing DNA cleavage properties and cancer cell growth inhibitory properties are also discussed. More importantly, the strongest pharmacological molecules are identified based on the inhibitory properties, cytotoxic values, and pharmacokinetics of synthesized derivatives. Additionally, a structure-activity relationship is established amongst the evaluated molecules. Supplemented by the mechanism of action in few pharmacological activities, the potent activity is also proved by the favorable binding interactions in molecular simulation studies.

Bidirectional control of mRNA translation and synaptic plasticity by the cytoplasmic polyadenylation complex.

Translational control of mRNAs in dendrites is essential for certain forms of synaptic plasticity and learning and memory. CPEB is an RNA-binding protein that regulates local translation in dendrites. Here, we identify poly(A) polymerase Gld2, deadenylase PARN, and translation inhibitory factor neuroguidin (Ngd) as components of a dendritic CPEB-associated polyadenylation apparatus. Synaptic stimulation induces phosphorylation of CPEB, PARN expulsion from the ribonucleoprotein complex, and polyadenylation in dendrites. A screen for mRNAs whose polyadenylation is altered by Gld2 depletion identified >100 transcripts including one encoding NR2A, an NMDA receptor subunit. shRNA depletion studies demonstrate that Gld2 promotes and Ngd inhibits dendritic NR2A expression. Finally, shRNA-mediated depletion of Gld2 in vivo attenuates protein synthesis-dependent long-term potentiation (LTP) at hippocampal dentate gyrus synapses; conversely, Ngd depletion enhances LTP. These results identify a pivotal role for polyadenylation and the opposing effects of Gld2 and Ngd in hippocampal synaptic plasticity.

Newborn Screening for Five Conditions in a Tertiary Care Government Hospital in Bengaluru, South India-Three Years Experience.

PURPOSE: Newborn screening is the need of the hour in a developing country like India as there is paucity of data from studies conducted in government hospitals with large sample size. The purpose of the study is to estimate incidence rate and recall rates for five conditions screened in the neonatal period namely congenital hypothyroidism, congenital adrenal hyperplasia, glucose-6-phosphate dehydrogenase (G6PD) deficiency, galactosemia and phenyl ketonuria (PKU). METHODS: The study was conducted at VaniVilas Hospital attached to Bangalore Medical College and Research Institute. A retrospective analysis of the results of newborn screening programme during a 3-year period between January 2016 and December 2018 was done. There were 47 623 livebirths during this period out of which 41 027 babies were screened (coverage-86% of total livebirths). Heelprick samples after 48 h of life and prior to discharge were analysed by quantitative assessment. Neonates having positive screening results were recalled by telephonic call for repeat screening and confirmatory tests. RESULTS: G6PD deficiency was the most common disorder with an incidence of 1:414, followed by congenital hypothyroidism and Congenital Adrenal Hyperplasia with an incidence of 1:2735 and 1:4102, respectively. Galactosemia and PKU were found to be rare in our population. The overall average recall rate was 0.6% which meant that 24 normal newborns were recalled for testing for one confirmed case. The recall rate was relatively higher for galactosemia and G6PD deficiency which was at 0.25% each compared to the other conditions where it was below 0.05%. CONCLUSION: The results of the study emphasize the need for universal newborn screening especially in all government hospitals with large birth cohorts.

The MAZ transcription factor is a downstream target of the oncoprotein Cyr61/CCN1 and promotes pancreatic cancer cell invasion via CRAF-ERK signaling.

Myc-associated zinc-finger protein (MAZ) is a transcription factor with dual roles in transcription initiation and termination. Deregulation of MAZ expression is associated with the progression of pancreatic ductal adenocarcinoma (PDAC). However, the mechanism of action of MAZ in PDAC progression is largely unknown. Here, we present evidence that MAZ mRNA expression and protein levels are increased in human PDAC cell lines, tissue samples, a subcutaneous tumor xenograft in a nude mouse model, and spontaneous cancer in the genetically engineered PDAC mouse model. We also found that MAZ is predominantly expressed in pancreatic cancer stem cells. Functional analysis indicated that MAZ depletion in PDAC cells inhibits invasive phenotypes such as the epithelial-to-mesenchymal transition, migration, invasion, and the sphere-forming ability of PDAC cells. Mechanistically, we detected no direct effects of MAZ on the expression of K-Ras mutants, but MAZ increased the activity of CRAF-ERK signaling, a downstream signaling target of K-Ras. The MAZ-induced activation of CRAF-ERK signaling was mediated via p21-activated protein kinase (PAK) and protein kinase B (AKT/PKB) signaling cascades and promoted PDAC cell invasiveness. Moreover, we found that the matricellular oncoprotein cysteine-rich angiogenic inducer 61 (Cyr61/CCN1) regulates MAZ expression via Notch-1-sonic hedgehog signaling in PDAC cells. We propose that Cyr61/CCN1-induced expression of MAZ promotes invasive phenotypes of PDAC cells not through direct K-Ras activation but instead through the activation of CRAF-ERK signaling. Collectively, these results highlight key molecular players in PDAC invasiveness and may help inform therapeutic strategies to improve clinical management and outcomes of PDAC.

Tinkering with targeting nucleotide signaling for control of intracellular Leishmania parasites.

Nucleotides are one of the most primitive extracellular signalling molecules across all phyla and regulate a multitude of responses. The biological effects of extracellular nucleotides/sides are mediated via the specific purinergic receptors present on the cell surface. In mammalian system, adenine nucleotides are the predominant nucleotides found in the extracellular milieu and mediate a constellation of physiological functions. In the context of host-pathogen interaction, extracellular ATP is recognized as a danger signal and potentiates the release of pro-inflammatory mediators from activated immune cells, on the other hand, its breakdown product adenosine exerts potential anti-inflammatory and immunosuppressive actions. Therefore, it is increasingly apparent that the interplay between extracellular ATP/adenosine ratios has a significant role in coordinating the regulation of the immune system in health and diseases. Several pathogens express ectonucleotidases on their surface and exploit the purinergic signalling as one of the mechanisms to modulate the host immune response. Leishmania pathogens are one of the most successful intracellular pathogens which survive within host macrophages and manipulate protective Th1 response into disease promoting Th2 response. In this review, we discuss the regulation of extracellular ATP and adenosine levels, the role of ATP/adenosine counter signalling in regulating the inflammation and immune responses during infection and how Leishmania parasites exploit the purinergic signalling to manipulate host response. We also discuss the challenges and opportunities in targeting purinergic signalling and the future prospects.

Reversible inhibition of PSD-95 mRNA translation by miR-125a, FMRP phosphorylation, and mGluR signaling.

The molecular mechanism for how RISC and microRNAs selectively and reversibly regulate mRNA translation in response to receptor signaling is unknown but could provide a means for temporal and spatial control of translation. Here we show that miR-125a targeting PSD-95 mRNA allows reversible inhibition of translation and regulation by gp1 mGluR signaling. Inhibition of miR-125a increased PSD-95 levels in dendrites and altered dendritic spine morphology. Bidirectional control of PSD-95 expression depends on miR-125a and FMRP phosphorylation status. miR-125a levels at synapses and its association with AGO2 are reduced in Fmr1 KO. FMRP phosphorylation promotes the formation of an AGO2-miR-125a inhibitory complex on PSD-95 mRNA, whereas mGluR signaling of translation requires FMRP dephosphorylation and release of AGO2 from the mRNA. These findings reveal a mechanism whereby FMRP phosphorylation provides a reversible switch for AGO2 and microRNA to selectively regulate mRNA translation at synapses in response to receptor activation.

N-Butyldeoxygalactonojirimycin Induces Reversible Infertility in Male CD Rats.

This study shows for the first time that an iminosugar exerts anti-spermiogenic effect, inducing reversible infertility in a species that is not related to C57BL/6 male mice. In CD rats, N-butyldeoxygalactonojirimycin (NB-DGJ) caused reversible infertility at 150 mg/kg/day when administered daily as single oral dose. NB-DGJ inhibited CD rat-derived testicular ß-glucosidase 2 (GBA2) activity at 10 µM but did not inhibit CD rat-derived testicular ceramide-specific glucosyltransferase (CGT) at doses up to 1000 µM. Pharmacokinetic studies revealed that sufficient plasma levels of NB-DGJ (50 µM) were achieved to inhibit the enzyme. Fertility was blocked after 35 days of treatment and reversed one week after termination of treatment. The rapid return of fertility indicates that the major effect of NB-DGJ may be epididymal rather than testicular. Collectively, our in vitro and in vivo studies in rats suggest that iminosugars should continue to be pursued as potential lead compounds for development of oral, non-hormonal male contraceptives. The study also adds evidence that GBA2, and not CGT, is the major target for the contraceptive effect of iminosugars.

Clinical Profile of Amitraz Poisoning.

AIMS OF THE STUDY: To study clinical presentation, complications and response to supportive management of Amitraz poisoning. METHODS AND MATERIAL: Fifty cases of acute Amitraz poisoning were studied in detail and compared with previous data from literature. RESULTS: All the fifty cases were brought to Dr. V.M. Govt. Medical college, among them thirty one cases were males and nineteen were females, with their age ranging from 14 years to 62 years. Mode of intoxication was oral route. Twenty cases were farmers. Two cases had accidental poisoning. The ingested amount was ranging from 10ml to 80 ml. Vomiting and nausea were the prominent symptoms, next were dizziness, lethargy, respiratory distress and pain abdomen. Hyperglycemia, glycosuria, were commonest manifestations. Three cases were treated with mechanical ventilation. All the cases responded to supportive treatment and recovered completely. CONCLUSION: Vomiting and nausea were the commonest symptoms. Hyperglycemia and glycosuria was commonest sign. There was good response to supportive treatment. There was no complication and no mortality.

Study of the Role of Salivary Lactate Dehydrogenase in Habitual Tobacco Chewers, Oral Submucous Fibrosis and Oral Cancer as a Biomarker.

AIM: To evaluate the salivary lactate dehydrogenase (LDH) levels in clinico-pathologically confirmed oral submucous fibrosis (OSMF), oral cancer and clinically diagnosed tobacco pouch keratosis patients. MATERIALS AND METHODS: A prospective, comparative study was carried out in a tertiary healthcare centre located in Loni from October 2013 to January 2014. A total of 120 patients were separated into 4 groups depending upon the clinical diagnosis as follows. Group I: healthy control (with no addictions and diseases). Group II: oral cancer. Group III: oral submucous fibrosis. Group IV: habitual tobacco chewers (tobacco addiction without any disease). Substantiation was done using biopsy. The samples were inspected for salivary LDH levels by the technique in line with the recommendations of the International Federation of Clinical Chemistry with the help of Erba Chem semi auto analyser. RESULTS: The mean salivary LDH levels in the control, oral cancer OSMF and habitual tobacco chewer group were 86.12 ± 7.05 IU/L, 592.09 ± 28.57 IU/L, 350.43 ± 5.90 IU/L and 125.19 ± 13.42 IU/L, respectively. Out of 4 groups, LDH activity was increased in saliva of patients with tobacco pouch keratosis, OSMF, and oral cancer consistently. Notable difference was found in the mean salivary levels of the above groups. Results were subjected to appropriate statistical analysis: one-way ANOVA, Student's unpaired t test for group-wise comparison followed by post hoc Tukey's test. CONCLUSION: We observed congruous higher levels of salivary LDH in oral precancer and cancer, and hence it could be a future marker.

Quality, safety and efficacy profiling of ginseng adventitious roots produced in vitro.

Ginseng (Panax ginseng C. A. Meyer, Family Araliaceae) is one of the major medicinal and nutraceutical plants, which is native to oriental region. It is used worldwide as a popular herbal medicine because of its pharmacological effects like anti-oxidative, anti aging, anti-cancer, adaptogenic, and other health-improving activities. Chief components of ginseng identified till date are ginsenosides, a group of saponins with triterpenoid structure. Ginseng is cultivated under controlled conditions, and for harvesting of fully grown roots of the plant, the cultivation takes long duration of about 5-7 years and cultivated ginseng roots are inferior in quality and ginsenoside content. Wild Mountain ginseng is superior in quality and ginsenoside content but is scarce in nature. Therefore, for obtaining the useful compounds of this plant at commercial scale, cell and organ cultures especially adventitious roots have been established by using superior clones of wild mountain ginseng, ginseng biomass is produced by applying large scale bioreactors. In this paper, an effort has been made to shed light on the scientific literature and to decipher the evidences for quality, safety, and efficacy of ginseng adventitious roots produced from in vitro cultures.

Hepatitis E infection in Odisha, India: A descriptive analysis.

Up to 25% of hepatitis E virus (HEV)-infected pregnant women in their third trimester die. Despite HEV being an important cause of viral hepatitis, no robust surveillance exists in India. We reviewed jaundice outbreaks records and hospital records from jaundiced individuals seeking treatment and linked those records to laboratory results (HEV immunoglobulin M enzyme-linked immunosorbent assay) for January 2012 to September 2013 in Odisha state. A total of 14 HEV confirmed outbreaks were identified, of which 33% of 139 jaundiced cases were HEV positive. There were two deaths. An additional 495 jaundiced cases were identified through hospital records, of which 18% were HEV positive. Among HEV-positive women (n = 35), 34% were of childbearing age. While one may not be able to generalize our results, this finding suggests HE is widespread in Odisha and may represent hidden disease burden in this region. The policymakers should monitor HEV infections in similar geographical areas, especially among population of childbearing age women to initiate evidence-based control measures.

Effect of Cocaine on Pulmonary Vascular Remodeling and Hemodynamics in Human Immunodeficiency Virus-Transgenic Rats.

Human immunodeficiency virus (HIV)-related pulmonary arterial hypertension has been found to be more prevalent in intravenous drug users. Our earlier cell-culture findings reported down-regulation of bone morphogenetic protein receptors (BMPRs) in combination with enhanced proliferation of human pulmonary arterial smooth muscle cells (PASMCs) in the presence of HIV-Trans-activator of transcription (Tat) and cocaine compared with either treatment alone. Here, we report physiologic evidence of significant increases in mean pulmonary arterial pressure in HIV-transgenic (Tg) rats intraperitoneally administered 40 mg/kg body weight cocaine (HIV-cocaine group) once daily for 21 days when compared with HIV-Tg rats given saline (HIV group) or wild-type (WT) Fischer 334 rats treated with (WT-cocaine group) and without cocaine (WT group). In addition, right ventricle systolic pressure was also found to be significantly higher in the HIV-cocaine rats compared with the WT group. Significant down-regulation in protein expression of BMPR-2 and BMPR-1B was observed in total lung extract from HIV-cocaine rats compared with the other three groups. Furthermore, the PASMCs isolated from HIV-cocaine rats demonstrated a higher level of proliferation and lower levels of apoptosis compared with cells isolated from other rat groups. Interestingly, corroborating our earlier cell-culture findings, we observed higher expression of BMPR-2 and BMPR-1B messenger RNA and significantly lower levels of BMPR-2 and BMPR-1B protein in HIV-cocaine PASMCs compared with cells isolated from all other groups. In conclusion, our findings support an additive effect of cocaine and HIV on smooth muscle dysfunction, resulting in enhanced pulmonary vascular remodeling with associated elevation of mean pulmonary arterial pressure and right ventricle systolic pressure in HIV-Tg rats exposed to cocaine.

MicroRNA Expression Signatures During Malignant Progression From Barrett's Esophagus.

The rapid increase and poor survival of esophageal adenocarcinoma (EAC) have led to significant efforts to promote early detection. Given that the premalignant lesion of Barrett's esophagus (BE) is the major known risk factor for EAC, multiple investigators have studied biomarker signatures that can predict malignant progression of BE to EAC. MicroRNAs, a novel class of gene regulators, are small non-coding RNAs and have been associated with carcinogenesis. MicroRNAs are ideal biomarkers because of their remarkable stability in fixed tissues, a common method for collection of clinical specimens, and in blood either within exosomes or as microRNA-protein complexes. Multiple studies show potential of microRNAs as tissue and blood biomarkers for diagnosis and prognosis of EAC but the results need confirmation in prospective studies. Although head-to-head comparisons are lacking, microRNA panels require less genes than messenger RNA panels for diagnosis of EAC in BE. MicroRNA diagnostic panels will need to be compared for accuracy against global measures of genome instability that were recently shown to be good predictors of progression but require sophisticated analytic techniques. Early studies on blood microRNA panels are promising but have found microRNA markers to be inconsistent among studies. MicroRNA expression in blood is different between various microRNA sub-compartments such as exosomes and microRNA-protein complexes and could affect blood microRNA measurements. Further standardization is needed to yield consistent results. We have summarized the current understanding of the tissue and blood microRNA signatures that may predict the development and progression of EAC.