Porous Organic Polymer-Based Nanocomposites for Hypoxia Relieving and Enhanced Chemotherapy in Hepatocellular Carcinoma.

Uncontrolled proliferation and altered metabolism of cancer cells result in an imbalance of nutrients and oxygen supply, and persuade hypoxia. Hypoxia, in turn, activates the transcription gene HIF-1α, which eventually upregulates the efflux transporter P-gp and induces multidrug resistance (MDR). Thus, hypoxia leads to the development of resistance to conventional therapies. Therefore, the fabrication of a nanoscale porous system enriched with upconversion nanoparticles to target cancer cells, evade hypoxia, and enhance anticancer therapy is the key goal of this article. Herein, upconversion nanoparticles are embedded in a nanoscale porous organic polymer (POP) and further conjugated with a targeting moiety and a catalase molecule. The nanoscale POP embedded in UCNPs is generated at room temperature. The targeting ligand, lactobionic acid, is attached after polymer coating, which effectively targets liver cancer cells. Then, catalase is grafted effectively to produce oxygen. Endogenously generated oxygen alleviates hypoxia in liver cancer cells. The drug- and catalase-loaded composite exhibit greater cytotoxicity in hypoxic liver cells than in normal cells by overcoming hypoxia and downregulating the hypoxia-inducible factors.

Stabilized Astaxanthin Nanoparticles Developed Using Flash Nanoprecipitation to Improve Oral Bioavailability and Hepatoprotective Effects.

In this study, we developed stabilized astaxanthin (AX) nanoparticles (sNP/AX) to improve the physicochemical properties, oral bioavailability, and hepatoprotection of AX. A flash nanoprecipitation technique was used with a multi-inlet vortex mixer to prepare the sNP/AX. Vitamins E (VE) and C (VC) were used as co-stabilizers with poloxamer 407 as a stabilizer to inhibit the oxidative degradation of AX during sNP/AX formation and storage. VC stabilized AX in the aqueous phase during the preparation, whereas VE markedly improved the storage stability of sNP/AX, as evidenced by the AX contents remaining at 94 and 81% after 12 weeks of storage at 4 °C and 25 °C, respectively. The mean sNP/AX diameter was 215 nm, which resulted in higher AX release properties than those of crystalline AX. Rats, orally administered sNP/AX (33.2 mg AX/kg), exhibited higher systemic exposure to AX, whereas oral absorption in the crystalline AX group was negligible. In the rat hepatic injury model, oral pretreatment with sNP/AX (33.2 mg AX/kg) markedly attenuated hepatic damage, as shown by the histopathological analysis and reduced levels of plasma biomarkers for hepatic injury. These findings suggest that strategically including antioxidative additives in the sNP/AX has the potential to improve the physicochemical and nutraceutical properties of AX.

Total Synthesis of a Linear Tetrasaccharide Repeating Unit of Vibrio vulnificus MO6-24.

Herein, we report the total synthesis of a linear, conjugation-ready, tetrasaccharide repeating unit of Vibrio vulnificus MO6-24, which is composed of rare amino sugars such as l-quinovosamine and d-galactosamine uronic acid. The key challenges addressed here are the synthesis of rare deoxy amino sugars, installation of consecutive 1,2-cis glycosidic linkages, and late-stage oxidation. Total synthesis of the target molecule was completed via a longest linear sequence of 29 steps in an overall yield of 0.7% starting from l-rhamnose.

The efficacy of alpha-lipoic acid in the management of burning mouth syndrome: An updated systematic review of randomized controlled clinical trials.

Background and Aims: Burning mouth syndrome (BMS) causes burning or uncomfortable feelings in the oral cavity without any obvious injuries. This condition's etiopathogenesis is still unknown, consequently, BMS management is very challenging. Alpha-lipoic acid (ALA) is a naturally occurring potent bioactive compound that has been found to be useful in the management of BMS in many studies. Therefore, we conducted a comprehensive systematic review to investigate the usefulness of ALA in the management of BMS based on randomized controlled trials (RCTs). Methods: Different electronic databases, including PubMed, Scopus, Embase, Web of Science, and Google Scholar, were extensively searched to find relevant studies. Results: This study included nine RCTs that matched the inclusion criteria. In most studies, ALA was given at a dose of 600-800 mg/day, with up to two months of follow-up. The majority of studies (six out of nine studies) indicated that ALA was more effective in BMS patients than in the placebo-controlled group. Conclusions: This comprehensive systematic review provides evidence of the positive outcomes of the treatment of BMS with ALA. However, more research might be needed before ALA can be considered the first-line therapy for BMS.

Lysophosphatidylcholine-based liposome to improve oral absorption and nephroprotective effects of astaxanthin.

BACKGROUND: The present study was aimed to develop astaxanthin (AX)-loaded liposomes by the utilization of soybean phosphatidylcholine (PC) and lysophosphatidylcholine (LPC) to improve the nutraceutical properties of AX. AX-loaded liposomes consisting of PC (PC/AX) and LPC (LPC/AX) were evaluated in terms of particle size distribution, morphology, release characteristics, pharmacokinetic behavior, and nephroprotective effects in a rat model of acute kidney injury. RESULTS: PC/AX and LPC/AX had uniform size distributions with a mean particle size of 254 and 148 nm, respectively. Under pH 6.8 conditions, both liposomes exhibited improved dissolution behavior of AX compared with crystalline AX (cAX). In particular, LPC/AX showed a sevenfold higher release of AX than PC/AX. After the oral administration of LPC/AX (33.2 mg AX kg-1 ) to rats, there was a significant increase in systemic exposure to AX, as evidenced by a 15-fold higher AUC0-24 h than PC/AX. However, the oral absorption of AX in the cAX group was negligible. Based on the results of histological analysis and measurement of plasma biomarkers, LPC/AX exhibited improved nephroprotective effects of AX in the rat model of kidney injury. CONCLUSION: From these observations, a strategic application of the LPC-based liposomal approach might be a promising option to improve the nutraceutical properties of AX. © 2022 Society of Chemical Industry.

Zinc status and coronary artery disease: A systematic review and meta-analysis.

BACKGROUND: The association between serum zinc (Zn) levels and coronary artery disease (CAD) has been elucidated, but no previous meta-analysis was done to provide firm evidence. Therefore, this systematic review and meta-analysis was aimed to investigate the possible association between serum Zn levels and CAD patients. METHODS: Relevant studies were identified using various electronic databases (PubMed, Scopus, Embase, Google Scholar, and Web of Science) searching up to May 2021. The Review Manager V5.3 was used to calculate the pooled standard mean difference (SMD) with the corresponding 95 % confidence interval (CI) using the random-effects model. RESULTS: A total of 10 studies with 614 cases (CAD patients) and 508 controls were included in this meta-analysis based on inclusion and exclusion criteria. The pooled results of the meta-analysis showed that CAD patients had significantly lower levels of Zn [SMD (95 % CI): -3.76 (-5.21, -2.31), Z = 5.08, P < 0.00001; I2= 98 %, P < 0.00001] compared with control subjects. The statistical evaluations of Begg's and Egger's tests indicated that there was no publication bias. CONCLUSION: The findings of the meta-analysis suggest that relatively low levels of Zn might have a potential role in the pathogenesis of CAD. Furthermore, large-scale observational studies are highly recommended in order to fully understand the association between Zn status and CAD.

Molecular insight into arsenic uptake, transport, phytotoxicity, and defense responses in plants: a critical review.

MAIN CONCLUSION: A critical investigation into arsenic uptake and transportation, its phytotoxic effects, and defense strategies including complex signaling cascades and regulatory networks in plants. The metalloid arsenic (As) is a leading pollutant of soil and water. It easily finds its way into the food chain through plants, more precisely crops, a common diet source for humans resulting in serious health risks. Prolonged As exposure causes detrimental effects in plants and is diaphanously observed through numerous physiological, biochemical, and molecular attributes. Different inorganic and organic As species enter into the plant system via a variety of transporters e.g., phosphate transporters, aquaporins, etc. Therefore, plants tend to accumulate elevated levels of As which leads to severe phytotoxic damages including anomalies in biomolecules like protein, lipid, and DNA. To combat this, plants employ quite a few mitigation strategies such as efficient As efflux from the cell, iron plaque formation, regulation of As transporters, and intracellular chelation with an array of thiol-rich molecules such as phytochelatin, glutathione, and metallothionein followed by vacuolar compartmentalization of As through various vacuolar transporters. Moreover, the antioxidant machinery is also implicated to nullify the perilous outcomes of the metalloid. The stress ascribed by the metalloid also marks the commencement of multiple signaling cascades. This whole complicated system is indeed controlled by several transcription factors and microRNAs. This review aims to understand, in general, the plant-soil-arsenic interaction, effects of As in plants, As uptake mechanisms and its dynamics, and multifarious As detoxification mechanisms in plants. A major portion of this article is also devoted to understanding and deciphering the nexus between As stress-responsive mechanisms and its underlying complex interconnected regulatory networks.

Synthesis and Application of Rare Deoxy Amino l-Sugar Analogues to Probe Glycans in Pathogenic Bacteria.

Bacterial cell envelope glycans are compelling antibiotic targets as they are critical for strain fitness and pathogenesis yet are virtually absent from human cells. However, systematic study and perturbation of bacterial glycans remains challenging due to their utilization of rare deoxy amino l-sugars, which impede traditional glycan analysis and are not readily available from natural sources. The development of chemical tools to study bacterial glycans is a crucial step toward understanding and altering these biomolecules. Here we report an expedient methodology to access azide-containing analogues of a variety of unusual deoxy amino l-sugars starting from readily available l-rhamnose and l-fucose. Azide-containing l-sugar analogues facilitated metabolic profiling of bacterial glycans in a range of Gram-negative bacteria and revealed differential utilization of l-sugars in symbiotic versus pathogenic bacteria. Further application of these probes will refine our knowledge of the glycan repertoire in diverse bacteria and aid in the design of novel antibiotics.

The prevalence of hepatitis B virus infection in Bangladesh: a systematic review and meta-analysis.

Despite the availability of an effective vaccine, hepatitis B virus (HBV) infection is one of the major public health problems worldwide, mostly in developing countries. This systematic review and meta-analysis were performed to estimate the pooled prevalence of HBV infection in Bangladesh. We systematically searched various electronic databases to retrieve relevant studies published until April 2021. A total of 15 studies were met the inclusion criteria and included in the meta-analysis. The pooled estimated prevalence of HBV infection in the general population of Bangladesh from 1995 to 2017 was 4.0% [95% confidence interval (CI) 3.0-5.1]. The results of subgroup analysis revealed that the prevalence of hepatitis B was higher in females than males [odds ratio (OR) 1.20, 95% CI 0.48-2.97, P = 0.70], people of age <25 years had a higher prevalence than people of age >25 years (OR 1.25, 95% CI 0.72-2.17, P = 0.42) and married people had a higher prevalence than unmarried/single people (OR 2.16, 95% CI 1.51-3.10, P < 0.0001). The Egger's test statistics (P = 0.584), Begg and Mazumdar's rank correlation test (P = 0.054) indicated the absence of publication bias. This study analysis reported a low intermediate prevalence of HBV infection (4%) in Bangladesh, which is currently higher than the global prevalence of HBV infection (3.5%).

A potent cadmium bioaccumulating Enterobacter cloacae strain displays phytobeneficial property in Cd-exposed rice seedlings.

In agricultural soil, cadmium (Cd) pollution compromises soil health, reduces crop yield, and produces Cd-contaminated crops. Bio-based approaches are necessary as an eco-friendly and sustainable solution to mitigate Cd-polluted areas. A heavy metal-resistant rhizobacterial strain (AS10) has been isolated from a heavy metal-defiled rice field. The 16S rDNA sequence and MALDI-TOF MS analyses of ribosomal protein reveal its identity closely similar to Enterobacter cloacae. The strain was found to withstand up to 4000 µg/ml Cd2+, 3312 µg/ml Pb2+ and 1500 µg/ml As3+. The Cd2+ removal efficiency was recorded as high as 72.11% when grown in 4000 µg/ml Cd2+. The strain's Cd-accumulation efficiency was also apprehended by TEM-EDAX followed by XRD-XRF-FTIR analyses. Besides, the strain showed solubilization of inorganic phosphate, ACC deaminase activity, nitrogen fixation and IAA production ability. Added further, the strain, as an efficient bioinoculant, significantly improved rice plant growth at the seedling stage through Cd immobilization. It prevented the surge of stress ethylene and oxidative stress in rice seedlings, resulting in overall plant growth improvement. Hence, the strain AS10 as potent plant growth-promoting rhizobacteria (PGPR) may be beneficial, especially in heavy metal-contaminated crop fields.

Total Synthesis of the Repeating Unit of Streptococcus pneumoniae Zwitterionic Polysaccharide Sp1.

Reported herein is the total synthesis of the trisaccharide repeating unit of Streptococcus pneumoniae zwitterionic polysaccharide Sp1 containing a rare sugar, 2-acetamido-4-amino-2,4,6-trideoxy-d-galactose (AAT), and three consecutive 1,2-cis-glycosidic linkages. The total synthesis was completed via highly stereoselective glycosylations and late-stage oxidation as key steps involving a longest linear sequence of 21 steps with 4.4% overall yield.

The association of oxidative stress biomarkers with type 2 diabetes mellitus: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Oxidative stress plays a major role in the development of type 2 diabetes mellitus (T2DM). However, there were controversial outcomes in the literature between the association of oxidative stress biomarkers and T2DM. The purpose of this systematic review and meta-analysis was to critically examine the association of oxidative stress biomarkers with T2DM. METHODS: We systematically searched different electronic databases including PubMed/Medline, EMBASE, ScienceDirect, Web of Science, and Cochrane Library to find the relevant studies up to May 2021. The pooled standard mean difference (SMD) with a 95% confidence interval (CI) was used to define the variation between the study groups. RESULTS: A total of 22 case-control studies with 2853 subjects (1667 diabetic patients and 1186 healthy controls) were found to be eligible for this meta-analysis. The pooled results of meta-analysis showed a significant difference in the levels malondialdehyde (SMD [95% CI]: 2.27 [1.62, 2.91]), nitric oxide (SMD [95% CI]: 1.40 [0.00, 2.81]), glutathione (SMD [95% CI]: -1.76 [-2.94, -0.59]), and total antioxidant status (SMD [95% CI]: -1.40 [-2.28, -0.51]) between the patient group and healthy subjects, whereas no significant difference was observed in the superoxide dismutase levels (SMD [95% CI]: -1.20 [-2.55, 0.15]) and glutathione peroxidase levels (SMD [95% CI]: 0.07 [-2.80, 2.94]). CONCLUSION: The present analysis suggests that oxidative stress might have a potential role in the pathogenesis of T2DM in humans. However, further studies should be needed to elucidate the possible mechanism and strengthen this evidence.

Charge-transfer-induced 2D ferromagnetism and realization of thermo-remnant memory effect in ultrathinß-NiOOH-encapsulated graphene.

For graphene-based 2D materials, charge transfer at the interface between graphene and ferromagnetic metal leads to many intriguing phenomena. However, because of the unidirectional spin orientation in ferromagnetic transition metals, interface interaction plays a detrimental role in diminishing the magnetic parameters on 2D surfaces. To overcome this issue, we have synthesized ultrathin 2D weak antiferromagneticß-NiOOH layers on a graphene surface. By exploiting the charge transfer effect and tuning the thickness of the thinß-NiOOH layers, conversion of ferromagnetism along with giant coercivity and the thermo-remnant magnetic memory effect were observed. As antiferromagnets have two spin orientations, transfer of charge at the interface breaks the nullifying effect of zero magnetization in antiferromagnets and the combined system behaves like a 2D ferrimagnet. Whenever, the sandwich structure ofß-NiOOH/graphene/ß-NiOOH is formed, it also shows interlayer exchange coupling those results in huge exchange bias and anomalous temperature dependence of coercivity. Due to the strong exchange interaction between the layers, the combined system also shows a robust temperature-based memory effect. Spin-polarized density functional theory was also calculated to confirm the interface interaction and its quantitative evaluation by means of Bader charge analysis and charge-density mapping.

Reproductive biology of mud crabs (Scylla olivacea) collected from Paikgachha, Khulna, Bangladesh.

OBJECTIVE: This study was carried out to estimate the sex ratio, maturity size, gonadosomatic index (GSI), and peak breeding season of mud crabs. MATERIALS AND METHODS: Samples were collected randomly from the estuary and river of the study area. Sampling was carried out monthly from April to September at every full moon during one high tide. A total number of 240 specimens were sampled, where 53 individuals were hermaphrodite. The crabs were shifted alive to the biology and histology lab for detailed biological study. Sex was determined. Male and female sex ratio and breeding season were also investigated. RESULTS: The male:female ratio was 1:0.96 and the ovarian development was categorized into five stages based on internal observations, viz. immature (stage I), underdeveloped (stage II), early developed (stage III), late developed (stage IV), and mature (stage V). The maturity percentages were 37%, 19%, 13%, 11%, and 20%, respectively. 50% maturation was estimated at 82.36 mm internal carapace width (ICW). The highest mean GSI value was 7.97 ± 3.03. The mature stage was found in all the working periods. This shows that females have activated ovaries in all the working months, and the species are continuous breeders. A higher frequency of vitellogenic ovary and higher GSI value were found in September. The maximum GSI value was found in the size group 70-79 mm. CONCLUSION: The study shows that the capture from the wild sources of mud crabs without any regulation can threaten the population structure. The capture of female mud crabs should be more than 82.36 mm ICW, which will help conserve and protect young crabs.

Unraveling the heavy metal resistance and biocontrol potential of Pseudomonas sp. K32 strain facilitating rice seedling growth under Cd stress.

Heavy metal and metalloid toxicity in agricultural land needs special attention for crop production essential to feed increasing population globally. Plant growth-promoting rhizobacteria (PGPR) are native biological agents that have tremendous potential to augment crop production in contaminated fields. This study involves selection and identification (through 16S rRNA gene sequence and FAME analysis) of a potent Pseudomonas sp. (strain K32) isolated from a metal-contaminated rice rhizosphere, aimed to its application for sustainable agriculture. Apart from multi-heavy metal(loid) resistance (Cd2+, Pb2+ and As3+ upto 4000, 3800, 3700 µg/ml respectively) along with remarkable Cd bioaccumulation potential (∼90%), this strain showed IAA production, nitrogen-fixation and phosphate solubilization under Cd stress. This bioaccumulation efficiency coupled with PGP traits resulted in the significant enhancement of rice seedling growth under Cd stress. This positive impact of K32 strain was clearly manifested in morphological and biochemical improvements under Cd stress including successful root colonization with rice roots. Cd uptake was also reduced significantly in seedlings in presence of K32 strain. Together with all mentioned properties, K32 showed bio-control potential against plant pathogenic fungi viz. Aspergillus flavus, Aspergillus parasiticus, Paecilomyces sp., Cladosporium herbarum, Rhizopus stolonifer and Alternaria alternata which establish K32 strain a key player in effective bioremediation of agricultural fields. Biocontrol potential was found to be the result of enzymatic activities viz. chitinase, ß-1,3-glucanase and protease which were estimated as 8.17 ± 0.44, 4.38 ± 0.35 and 7.72 ± 0.28 U/mg protein respectively.

Abatement of arsenic-induced phytotoxic effects in rice seedlings by an arsenic-resistant Pantoea dispersa strain.

Population detonation and rapid industrialization are the major factors behind the reduction in cultivable land that affects crop production seriously. This situation is further being deteriorated due to the negative effects of abiotic stresses. Under such conditions, plant growth-promoting rhizobacteria (PGPR) are found to improve crop production which is essential for sustainable agriculture. This study is focused on the isolation of potent arsenic (As)-resistant PGPR from the agricultural land of West Bengal, India, and its application to reduce As translocation in rice seedlings. After screening, an As-resistant PGPR strain AS18 was identified by phenotypic characters and 16S rDNA sequence-based homology as Pantoea dispersa. This strain displayed nitrogen fixation, phosphate solubilization, 1-aminocyclopropane-1-carboxylic acid deaminase (ACCD) activity, indole-3-acetic acid (IAA) production, in addition to As (III) resistance up to 3750 µg/mL. The As removal efficiency of this strain was up to 93.12% from the culture medium as evidenced by AAS. The bioaccumulation property of AS18 strain was further validated by TEM-EDAX-XRD-XRF-FTIR studies. This strain showed significant morpho-biochemical improvements including antioxidant enzymatic activities and As-minimization in plant (rice) cells. Thus, being an As-resistant potent PGPR, AS18 strain is expected to be applied in As-spiked agricultural fields for bioremediation and phytostimulation.

Prevalence of chronic kidney disease in Bangladesh: a systematic review and meta-analysis.

BACKGROUND: Worldwide, chronic kidney disease (CKD) is a major public health issue, with a leading cause of death and disability. The aim of our study to estimate the prevalence of CKD in the Bangladeshi population based on existing data of previous studies. METHODS: In this systematic review and meta-analysis study, electronic search engines of PubMed, Google Scholar, Scopus, and the national journal databases were used to find relevant published articles until December 31, 2019. Based on predefined inclusion/exclusion criteria, nine studies were included, and RevMan V5.0 statistical software was used for meta-analysis. RESULTS: The outcomes of the included studies (nine studies, a total of 225,206 participants) based on meta-analysis showed an overall prevalence of CKD in Bangladeshi people of 22.48%, which was higher than the global prevalence of CKD. The prevalence of CKD in females was higher with high heterogeneity (I2 90%) in contrast to male participants (25.32% vs. 20.31%). CONCLUSION: Above all, this study revealed a higher rate of prevalence of CKD in Bangladeshi people. So, it needs more attention to concern public health policymakers and the government to control and reduce the high-risk of disability due to CKD.

Evaluation of antinociceptive, antihyperglycemic, and membrane stabilizing activities of Garcinia lancifolia Roxb.

This study was undertaken to examine the antinociceptive, antihyperglycemic, and membrane stabilizing activity with phytochemical screening of methanolic extract of Garcinia lanceifolia whole plant. The extracts were subjected to in-vivo antinociceptive, antihyperglycemic activity in laboratory animals and in-vitro membrane stabilizing activity. In peripheral antinociceptive activity, G. lanceifolia (400 and 200 mg/kg) exhibited significant (P < 0.001) inhibition of writhing with 59.15% and 49.30% respectively comparable to standard Diclofenac (54.92% inhibition). In central antinociceptive activity, the extract (400 and 200 mg/kg) exhibited significant analgesic activity having 78.31% (P < 0.05) and 89.95% (P < 0.01) elongation of reaction time respectively in 90 min after administration of sample comparable to the standard Morphine (708.99% elongation). In hypoglycemic activity, the extract (400 and 200 mg/kg) exhibit statistically significant (P < 0.001) antihyperglycemic activity compared to standard drug Glibenclamide (10 mg/kg) at different time interval. In membrane stabilizing activity assay, clearly evident that the methanolic extracts of G. lanceifolia were highly effective to prevent the lyses of erythrocytes induced by heat. The outcomes of the present study revealed that this plant possess noteworthy pharmacological activities that may be basis for further research to disclose feasible mode of action of the plant part.

Application of Euclidean distance measurement and principal component analysis for gene identification.

Gene systems are extremely complex, heterogeneous, and noisy in nature. Many statistical tools which are used to extract relevant feature from genes provide fuzzy and ambiguous information. High-dimensional gene expression database available in public domain usually contains thousands of genes. Efficient prediction method is demanding nowadays for accurate identification of such database. Euclidean distance measurement and principal component analysis methods are applied on such databases to identify the genes. In both methods, prediction algorithm is based on homology search approach. Digital Signal Processing technique along with statistical method is used for analysis of genes in both cases. A two-level decision logic is used for gene classification as healthy or cancerous. This binary logic minimizes the prediction error and improves prediction accuracy. Superiority of the method is judged by receiver operating characteristic curve.

Ripening of fleshy fruit: molecular insight and the role of ethylene.

Development and ripening in fruit is a unique phase in the life cycle of higher plants which encompasses several stages progressively such as fruit development, its maturation, ripening and finally senescence. During ripening phase, several physiological and biochemical changes take place through differential expression of various genes that are developmentally regulated. Expression and/or suppression of these genes contribute to various changes in the fruit that make it visually attractive and edible. However, in fleshy fruit massive losses accrue during post harvest handling of the fruit which may run into billions of dollars worldwide. This encouraged scientists to look for various ways to save these losses. Genetic engineering appears to be the most promising and cost effective means to prevent these losses. Most fleshy fruit ripen in the presence of ethylene and once ripening has been initiated proceeds uncontrollably. Ethylene evokes several responses during ripening through a signaling cascade and thousands of genes participate which not only sets in ripening but also responsible for its spoilage. Slowing down post ripening process in fleshy fruit has been the major focus of ripening-related research. In this review article, various developments that have taken place in the last decade with respect to identifying and altering the function of ripening-related genes have been described. Role of ethylene and ethylene-responsive genes in ripening of fleshy fruit is also included. Taking clues from the studies in tomato as a model fruit, few case studies are reviewed.